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Younis M, Kumar P, Sudershan A, Gezici S, Angral C, Muruganantham B, Mohan G, Behlam I, Digra SK, Anand V. Serum level of carcinoembryonic antigen and risk of colorectal cancer: a case-control study from South Indian population. THE NUCLEUS 2025. [DOI: 10.1007/s13237-025-00543-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 02/11/2025] [Indexed: 05/04/2025] Open
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Bunyavanich S, Becker PM, Altman MC, Lasky-Su J, Ober C, Zengler K, Berdyshev E, Bonneau R, Chatila T, Chatterjee N, Chung KF, Cutcliffe C, Davidson W, Dong G, Fang G, Fulkerson P, Himes BE, Liang L, Mathias RA, Ogino S, Petrosino J, Price ND, Schadt E, Schofield J, Seibold MA, Steen H, Wheatley L, Zhang H, Togias A, Hasegawa K. Analytical challenges in omics research on asthma and allergy: A National Institute of Allergy and Infectious Diseases workshop. J Allergy Clin Immunol 2024; 153:954-968. [PMID: 38295882 PMCID: PMC10999353 DOI: 10.1016/j.jaci.2024.01.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 01/19/2024] [Accepted: 01/24/2024] [Indexed: 02/29/2024]
Abstract
Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprising investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states of the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes the major points and conclusions from this NIAID workshop. As a group, the investigators underscored the imperatives for rigorous analytic frameworks, integration of different omics data types, cross-disciplinary interaction, strategies for overcoming current limitations, and the overarching goal to improve scientific understanding and care of asthma and allergic diseases.
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Affiliation(s)
| | - Patrice M Becker
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Md
| | | | - Jessica Lasky-Su
- Brigham & Women's Hospital and Harvard Medical School, Boston, Mass
| | | | | | | | | | - Talal Chatila
- Boston Children's Hospital and Harvard Medical School, Boston, Mass
| | | | | | | | - Wendy Davidson
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Md
| | - Gang Dong
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Md
| | - Gang Fang
- Icahn School of Medicine at Mount Sinai, New York, NY
| | - Patricia Fulkerson
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Md
| | | | - Liming Liang
- Harvard T. H. Chan School of Public Health, Boston, Mass
| | | | - Shuji Ogino
- Brigham & Women's Hospital and Harvard Medical School, Boston, Mass; Harvard T. H. Chan School of Public Health, Boston, Mass; Broad Institute of MIT and Harvard, Boston, Mass
| | | | | | - Eric Schadt
- Icahn School of Medicine at Mount Sinai, New York, NY
| | | | - Max A Seibold
- National Jewish Health, Denver, Colo; University of Colorado School of Medicine, Aurora, Colo
| | - Hanno Steen
- Boston Children's Hospital and Harvard Medical School, Boston, Mass
| | - Lisa Wheatley
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Md
| | - Hongmei Zhang
- School of Public Health, University of Memphis, Memphis, Tenn
| | - Alkis Togias
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Md
| | - Kohei Hasegawa
- Massachusetts General Hospital and Harvard Medical School, Boston, Mass
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Lim SY, Ulaganathan V, Nallamuthu P, Gunasekaran B, Salvamani S. Dietary Patterns and Lifestyle Factors Associated with the Risk of Colorectal Cancer: A Hospital-Based Case-Control Study among Malaysians. Malays J Med Sci 2024; 31:212-234. [PMID: 38456114 PMCID: PMC10917583 DOI: 10.21315/mjms2024.31.1.18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 06/16/2023] [Indexed: 03/09/2024] Open
Abstract
Background This study aimed to examine the association between dietary patterns, lifestyle factors, and colorectal cancer (CRC) risk among the Malaysian population. Methods We recruited 100 patients and 100 controls from two selected government hospitals. Principal component analysis was used to identify dietary patterns using a 123-item semiquantitative food frequency questionnaire. Tobacco smoking and alcohol consumption questionnaires were modified from the WHO STEPS Survey questionnaire. Physical activity levels were assessed using the revised Global Physical Activity questionnaire. Associations between dietary patterns, lifestyle factors and CRC risk were assessed using logistic regression with SPSS version 24.0. Results Three dietary patterns were derived from factor analysis: i) vegetables; ii) meat, seafood and processed food; and iii) grains and legumes. High vegetable diet intake was independently and significantly associated with an 81% decreased risk of CRC (odds ratio [OR]: 0.19; 95% confidence interval [CI]: 0.08, 0.46). Both recreational-related physical activity (OR: 2.04; 95% CI: 1.14, 3.64) and vigorous physical activity (OR: 2.06; 95% CI: 1.13, 3.74) are significantly associated with decreased risk of CRC. Increasing the number of cigarettes smoked (≥ 16 cigarettes) per day significantly increased the odds of developing CRC (OR: 2.58; 95% CI: 1.95, 6.75). The duration of alcohol consumption cessation was inversely associated with CRC risk (OR: 2.52; 95% CI: 2.30, 10.57). Conclusion The protective effects of a fruit and vegetable diet, and a healthy lifestyle can be used to develop interventions that help reduce the risk of CRC in the Malaysian population.
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Affiliation(s)
- Sook Yee Lim
- Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia
| | | | | | | | - Shamala Salvamani
- Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur, Malaysia
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Zhao K, Li H, Zhang B, Pang W, Yan S, Zhao X, Liu X, Wang W, Han Q, Yao Y, Chu T, Feng Z, Zhang Q, Zhang C. Factors influencing advanced colorectal neoplasm anatomic site distribution in China: An epidemiological study based on colorectal cancer screening data. Cancer Med 2023; 12:22252-22262. [PMID: 37975155 PMCID: PMC10757099 DOI: 10.1002/cam4.6722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 10/31/2023] [Accepted: 11/07/2023] [Indexed: 11/19/2023] Open
Abstract
OBJECTIVE Existing studies indicate that advanced colorectal neoplasms exhibit distinct clinical and biological traits based on anatomical sites. However, in China, especially for advanced colorectal neoplasms, there's limited information available on these traits. Our primary objective is to comprehensively study the characteristics of advanced colorectal neoplasm patients in different anatomical sites in China. METHODS We selected information from the colorectal cancer screening database in Tianjin, China, since 2010 as the study subject. We chose valid information from 3113 patients with comprehensive data and diagnosed advanced colorectal neoplasms (ANs) from a pool of 19,308 individuals to be included in the study. We then conducted further analysis to examine the correlation between these epidemiological data and tumor location. RESULTS Among the 3113 patients, neoplasms in the left side of the colon accounted for the largest proportion, while neoplasms in the right side of the colon had the smallest proportion, followed by rectal neoplasms. The highest proportion of advanced colorectal neoplasms was found among men. In the age group of 39-49 years old, the proportion of left late-stage advanced colon neoplasms was equal to that of right late-stage advanced colon neoplasms, while late-stage advanced rectal neoplasms increased with age. Smoking, drinking, and a history of colon cancer in first-degree relatives showed statistically significant associations with the location distribution of advanced colorectal neoplasms. A history of appendicitis, appendectomy, cholecystitis, or cholecystectomy did not significantly affect the location distribution of advanced colorectal neoplasms. However, among patients with such histories, there was a statistically significant relationship between advanced colon neoplasms on the right and those on the left and in the rectum. Similar results were observed for BMI. CONCLUSION Our research findings demonstrate that advanced colorectal neoplasms display unique epidemiological characteristics depending on their anatomical locations, and these distinctions deviate from those observed in Western populations. These insights contribute to a more comprehensive understanding of the topic and offer valuable guidance for future research in China. We advocate for further investigations centered on the anatomical location of colorectal neoplasms to enhance the precision of colorectal cancer (CRC) screening and treatment.
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Affiliation(s)
- Kailong Zhao
- Department of Colorectal SurgeryTianjin Union Medical CenterTianjinChina
- School of MedicineNankai UniversityTianjinChina
| | - Hongzhou Li
- Department of GastroenterologyTianjin Union Medical CenterTianjinChina
| | - Baofeng Zhang
- Department of GastroenterologyTianjin Union Medical CenterTianjinChina
| | - Wenwen Pang
- Department of clinical laboratoryTianjin Union Medical CenterTianjinChina
| | - Suying Yan
- Department of Colorectal SurgeryTianjin Union Medical CenterTianjinChina
- School of Integrative MedicineTianjin University of Traditional Chinese MedicineTianjinChina
| | - Xinzhu Zhao
- Department of Colorectal SurgeryTianjin Union Medical CenterTianjinChina
- School of MedicineNankai UniversityTianjinChina
| | - Xinyu Liu
- Tianjin Medical UniversityTianjinChina
| | - Wanting Wang
- Department of Colorectal SurgeryTianjin Union Medical CenterTianjinChina
- School of Integrative MedicineTianjin University of Traditional Chinese MedicineTianjinChina
| | - Qiurong Han
- Department of Colorectal SurgeryTianjin Union Medical CenterTianjinChina
- School of Integrative MedicineTianjin University of Traditional Chinese MedicineTianjinChina
| | - Yao Yao
- Department of Colorectal SurgeryTianjin Union Medical CenterTianjinChina
- School of Integrative MedicineTianjin University of Traditional Chinese MedicineTianjinChina
| | - Tianhao Chu
- Department of Colorectal SurgeryTianjin Union Medical CenterTianjinChina
- School of Integrative MedicineTianjin University of Traditional Chinese MedicineTianjinChina
| | - Zhiqiang Feng
- Department of Colorectal SurgeryTianjin Union Medical CenterTianjinChina
- School of Integrative MedicineTianjin University of Traditional Chinese MedicineTianjinChina
| | - Qinghuai Zhang
- Department of Colorectal SurgeryTianjin Union Medical CenterTianjinChina
- The Institute of Translational MedicineTianjin Union Medical CenterTianjinChina
- Tianjin Institute of ColoproctologyTianjinChina
| | - Chunze Zhang
- Department of Colorectal SurgeryTianjin Union Medical CenterTianjinChina
- The Institute of Translational MedicineTianjin Union Medical CenterTianjinChina
- Tianjin Institute of ColoproctologyTianjinChina
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Nakano S, Yamaji T, Shiraishi K, Hidaka A, Shimazu T, Kuchiba A, Saito M, Kunishima F, Nakaza R, Kohno T, Sawada N, Inoue M, Tsugane S, Iwasaki M. Smoking and risk of colorectal cancer according to KRAS and BRAF mutation status in a Japanese prospective Study. Carcinogenesis 2023; 44:476-484. [PMID: 37352389 DOI: 10.1093/carcin/bgad046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 04/21/2023] [Accepted: 06/22/2023] [Indexed: 06/25/2023] Open
Abstract
Although smoking is a major modifiable risk factor for many types of cancer, evidence for colorectal cancer is equivocal in Asian populations. Recent Western studies have proposed that the association between smoking and colorectal cancer is restricted to specific tumor molecular subtypes. However, no studies have evaluated the association according to tumor molecular subtypes in Asian populations. In a Japanese prospective population-based cohort study of 18 773 participants, we collected tumor tissues from incident colorectal cancer cases and evaluated KRAS (Kirsten rat sarcoma viral oncogene homolog) and BRAF (v-raf murine sarcoma viral oncogene homolog B) mutation status using target sequencing. Multivariable-adjusted Cox proportional hazard model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of smoking with the risk of overall colorectal cancer and its subtypes defined by KRAS and BRAF mutation status. Among 339 cases, KRAS and BRAF mutations were identified in 164 (48.4%) and 16 (4.7%) cases, respectively. The multivariable-adjusted HR for ever smoking compared with never smoking was 1.24 [95% CI: 0.93-1.66], 1.75 [1.14-2.68], 0.87 [0.59-1.29], 1.24 [0.93-1.67] and 1.22 [0.38-3.93] for overall, KRAS wild-type, KRAS-mutated, BRAF wild-type and BRAF-mutated colorectal cancer, respectively. The statistically significant heterogeneity was indicated between KRAS mutation status (Pheterogeneity = 0.01) but not between BRAF mutation status. This study is the first to demonstrate that smokers have an approximately 2-fold higher risk of KRAS wild-type colorectal cancer than never smokers in an Asian population. Our findings support that smoking is a risk factor for colorectal cancer, especially for its subtype without KRAS mutations, in Asian populations.
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Affiliation(s)
- Shiori Nakano
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Taiki Yamaji
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Kouya Shiraishi
- Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan
| | - Akihisa Hidaka
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
- Division of Gastroenterology and Hepatology, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Taichi Shimazu
- Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Aya Kuchiba
- Graduate School of Health Innovation, Kanagawa University of Human Services, Kanagawa, Japan
- Division of Biostatistical Research, Institute for Cancer Control/Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Tokyo, Japan
| | - Masahiro Saito
- Department of Diagnostic Pathology, Hiraka General Hospital, Yokote, Akita, Japan
| | - Fumihito Kunishima
- Department of Diagnostic Pathology, Okinawa Prefecture Chubu Hospital, Okinawa, Japan
| | - Ryouji Nakaza
- Department of clinical laboratory, Nakagami Hospital, Okinawa, Japan
| | - Takashi Kohno
- Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan
| | - Norie Sawada
- Division of Cohort research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Manami Inoue
- Division of Prevention, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Shoichiro Tsugane
- Division of Cohort research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
- National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan
| | - Motoki Iwasaki
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
- Division of Cohort research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
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Gopalan V, Hannenhalli S. Towards a Synthesis of the Non-Genetic and Genetic Views of Cancer in Understanding Pancreatic Ductal Adenocarcinoma Initiation and Prevention. Cancers (Basel) 2023; 15:cancers15072159. [PMID: 37046820 PMCID: PMC10093726 DOI: 10.3390/cancers15072159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 03/22/2023] [Accepted: 03/27/2023] [Indexed: 04/14/2023] Open
Abstract
While much of the research in oncogenesis and cancer therapy has focused on mutations in key cancer driver genes, more recent work suggests a complementary non-genetic paradigm. This paradigm focuses on how transcriptional and phenotypic heterogeneity, even in clonally derived cells, can create sub-populations associated with oncogenesis, metastasis, and therapy resistance. We discuss this complementary paradigm in the context of pancreatic ductal adenocarcinoma. A better understanding of cellular transcriptional heterogeneity and its association with oncogenesis can lead to more effective therapies that prevent tumor initiation and slow progression.
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Affiliation(s)
- Vishaka Gopalan
- Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA
| | - Sridhar Hannenhalli
- Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA
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Wang H, Yuan Z, Wang S, Pang W, Wang W, Liu X, Yi B, Han Q, Yao Y, Zhang Q, Zhang X, Zhang C. The comparison of risk factors for colorectal neoplasms at different anatomical sites. Int J Colorectal Dis 2023; 38:26. [PMID: 36719544 PMCID: PMC9889414 DOI: 10.1007/s00384-022-04296-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/23/2022] [Indexed: 02/01/2023]
Abstract
AIM Both the clinical manifestation and molecular characteristics of colorectal cancer (CRC) vary according to the anatomical site. We explored the risk factors for four groups of colorectal neoplasms (CRN) at different anatomical sites. METHODS We extracted data from the database of Tianjin Colorectal Cancer Screening Program from 2010 to 2020. According to the CRN anatomical sites, patients were divided into four groups: the proximal colon group, the distal colon group, the rectum group, and the multiple colorectal sites. Binary logistic regression analysis was used to explore the differences in risk factors of CRN at different anatomical sites. RESULTS The numbers of patients with CRN in the proximal colon, distal colon, rectum, and multiple colorectal sites were 4023, 6920, 3657, and 7938, respectively. Male sex was associated with a higher risk from the proximal colon to the rectum. Advanced age and obesity were also significantly associated with overall colorectal CRN risk, but there were some differences between men and women. Smoking was associated with CRN risk only in the distal colon and rectum in both men and women. Frequent alcohol consumption and family history of CRC in first-degree relatives (FDRs) were associated with the risk of multisite colorectal CRN only in males. CONCLUSIONS We observed differences in advanced age, obesity, smoking, alcohol consumption, and family history of colorectal cancer at different anatomical sites of colorectal neoplasms. These factors vary by gender.
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Grants
- 19YFZCSY00420 The Key R&D Projects in the Tianjin Science and Technology Pillar Program
- 19YFZCSY00420 The Key R&D Projects in the Tianjin Science and Technology Pillar Program
- 19YFZCSY00420 The Key R&D Projects in the Tianjin Science and Technology Pillar Program
- 19YFZCSY00420 The Key R&D Projects in the Tianjin Science and Technology Pillar Program
- 19YFZCSY00420 The Key R&D Projects in the Tianjin Science and Technology Pillar Program
- 19YFZCSY00420 The Key R&D Projects in the Tianjin Science and Technology Pillar Program
- 19YFZCSY00420 The Key R&D Projects in the Tianjin Science and Technology Pillar Program
- 19YFZCSY00420 The Key R&D Projects in the Tianjin Science and Technology Pillar Program
- 19YFZCSY00420 The Key R&D Projects in the Tianjin Science and Technology Pillar Program
- 19YFZCSY00420 The Key R&D Projects in the Tianjin Science and Technology Pillar Program
- 19YFZCSY00420 The Key R&D Projects in the Tianjin Science and Technology Pillar Program
- 19YFZCSY00420 The Key R&D Projects in the Tianjin Science and Technology Pillar Program
- 21JCZDJC00060, 21JCYBJC00180 and 21JCYBJC00340 Natural Science Foundation of Tianjin
- 21JCZDJC00060, 21JCYBJC00180 and 21JCYBJC00340 Natural Science Foundation of Tianjin
- 21JCZDJC00060, 21JCYBJC00180 and 21JCYBJC00340 Natural Science Foundation of Tianjin
- 21JCZDJC00060, 21JCYBJC00180 and 21JCYBJC00340 Natural Science Foundation of Tianjin
- 21JCZDJC00060, 21JCYBJC00180 and 21JCYBJC00340 Natural Science Foundation of Tianjin
- 21JCZDJC00060, 21JCYBJC00180 and 21JCYBJC00340 Natural Science Foundation of Tianjin
- 21JCZDJC00060, 21JCYBJC00180 and 21JCYBJC00340 Natural Science Foundation of Tianjin
- 21JCZDJC00060, 21JCYBJC00180 and 21JCYBJC00340 Natural Science Foundation of Tianjin
- 21JCZDJC00060, 21JCYBJC00180 and 21JCYBJC00340 Natural Science Foundation of Tianjin
- 21JCZDJC00060, 21JCYBJC00180 and 21JCYBJC00340 Natural Science Foundation of Tianjin
- 21JCZDJC00060, 21JCYBJC00180 and 21JCYBJC00340 Natural Science Foundation of Tianjin
- 21JCZDJC00060, 21JCYBJC00180 and 21JCYBJC00340 Natural Science Foundation of Tianjin
- TJYXZDXK-044A Tianjin Key Medical Discipline (Specialty) Construction Project
- TJYXZDXK-044A Tianjin Key Medical Discipline (Specialty) Construction Project
- TJYXZDXK-044A Tianjin Key Medical Discipline (Specialty) Construction Project
- TJYXZDXK-044A Tianjin Key Medical Discipline (Specialty) Construction Project
- TJYXZDXK-044A Tianjin Key Medical Discipline (Specialty) Construction Project
- TJYXZDXK-044A Tianjin Key Medical Discipline (Specialty) Construction Project
- TJYXZDXK-044A Tianjin Key Medical Discipline (Specialty) Construction Project
- TJYXZDXK-044A Tianjin Key Medical Discipline (Specialty) Construction Project
- TJYXZDXK-044A Tianjin Key Medical Discipline (Specialty) Construction Project
- TJYXZDXK-044A Tianjin Key Medical Discipline (Specialty) Construction Project
- TJYXZDXK-044A Tianjin Key Medical Discipline (Specialty) Construction Project
- TJYXZDXK-044A Tianjin Key Medical Discipline (Specialty) Construction Project
- 2019ZZ07 Tianjin Hospital Association Hospital Management Research Project
- 2019ZZ07 Tianjin Hospital Association Hospital Management Research Project
- 2019ZZ07 Tianjin Hospital Association Hospital Management Research Project
- 2019ZZ07 Tianjin Hospital Association Hospital Management Research Project
- 2019ZZ07 Tianjin Hospital Association Hospital Management Research Project
- 2019ZZ07 Tianjin Hospital Association Hospital Management Research Project
- 2019ZZ07 Tianjin Hospital Association Hospital Management Research Project
- 2019ZZ07 Tianjin Hospital Association Hospital Management Research Project
- 2019ZZ07 Tianjin Hospital Association Hospital Management Research Project
- 2019ZZ07 Tianjin Hospital Association Hospital Management Research Project
- 2019ZZ07 Tianjin Hospital Association Hospital Management Research Project
- 2019ZZ07 Tianjin Hospital Association Hospital Management Research Project
- The Key R&D Projects in the Tianjin Science and Technology Pillar Program
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Affiliation(s)
- Huaqing Wang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China
- School of Medicine, Nankai University, Tianjin, China
| | - Zhen Yuan
- School of Medicine, Nankai University, Tianjin, China
| | - Shuyuan Wang
- School of Medicine, Nankai University, Tianjin, China
| | - Wenwen Pang
- Department of Clinical Laboratory, Tianjin Union Medical Center, Tianjin, China
| | - Wanting Wang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xinyu Liu
- Tianjin Medical University, Tianjin, China
| | - Ben Yi
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Qiurong Han
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yao Yao
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Qinghuai Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China
- The Institute of Translational Medicine, Tianjin Union Medical Center, Tianjin, China
- Tianjin Institute of Coloproctology, Tianjin, China
| | - Xipeng Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
- The Institute of Translational Medicine, Tianjin Union Medical Center, Tianjin, China.
- Tianjin Institute of Coloproctology, Tianjin, China.
| | - Chunze Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
- The Institute of Translational Medicine, Tianjin Union Medical Center, Tianjin, China.
- Tianjin Institute of Coloproctology, Tianjin, China.
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8
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Mitochondrial Factor C20orf7 Facilitates the EMT-Mediated Cancer Cell Migration and the Proliferation of Colon Cancer In Vitro and In Vivo. Genes (Basel) 2022; 13:genes13112111. [DOI: 10.3390/genes13112111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/10/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022] Open
Abstract
Colon cancer is a major malignant neoplasm with a low survival rate for late-stage patients. Therefore, the investigation of molecules regulating colon cancer progression and the discovery of novel therapeutic targets is critical. Mitochondria play a vital role in maintaining the homeostasis of cells. Abnormal mitochondrial metabolism alterations and the induction of glycolysis can facilitate tumor growth; therefore, targeting mitochondrial molecules is suggested to be a promising strategy for cancer treatment. In this study, we investigated the role of this largely unknown mitochondrial factor, chromosome 20 open reading frame 7 (C20orf7), in colon cancer progression. Clustered regularly interspaced short palindromic repeats (CRISPR) technology was utilized for C20orf7 depletion, and functional assays were performed to examine the regulation of C20orf7 in colon cancer cells. We demonstrated that C20orf7 facilitates epithelial–mesenchymal transition (EMT)-mediated cell migration and promotes the proliferation of colon cancer. The anti-cancer drug 5-fluorouracil (5FU) was also applied, and C20orf7 was targeted with a combination of 5FU treatment, which could further enhance the anti-cancer effect in the colon cancer cell line and the xenograft mice model. In summary, this study demonstrated, for the first time, that C20orf7 plays a promotional role in cancer tumorigenesis and could be a promising therapeutic target in colon cancer treatment.
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9
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Wang L, Knudsen MD, Lo CH, Wang K, He M, Polychronidis G, Hang D, He X, Zhong R, Wu K, Chan AT, Ogino S, Giovannucci EL, Song M. Adherence to a healthy lifestyle in relation to colorectal cancer incidence and all-cause mortality after endoscopic polypectomy: A prospective study in three U.S. cohorts. Int J Cancer 2022; 151:1523-1534. [PMID: 35716133 PMCID: PMC9474593 DOI: 10.1002/ijc.34176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 05/30/2022] [Accepted: 05/31/2022] [Indexed: 11/07/2022]
Abstract
It remains unknown whether maintenance of a healthy lifestyle after endoscopic polypectomy could still confer benefit for colorectal cancer (CRC) incidence and mortality. In this study, we defined a healthy lifestyle score based on body mass index, smoking, physical activity, alcohol consumption and diet (range, 0-5). We used Cox proportional hazards regression to estimate the hazard ratios (HRs) for the associations of healthy lifestyle score and individual lifestyle factors with CRC incidence and all-cause mortality. During a median of 10 years of follow-up of 24 668 participants who underwent endoscopic polypectomy, we documented 161 CRC cases and 4857 all-cause deaths. A higher healthy lifestyle score after endoscopic polypectomy was associated with lower risk of CRC and all-cause mortality. Compared with individuals with 0 to 1 healthy lifestyle factors, those with 2, 3 and 4 to 5 healthy lifestyle factors had a HR for CRC risk of 0.86 (95% confidence interval [CI], 0.60-1.24), 0.73 (95% CI, 0.47-1.14) and 0.52 (95% CI, 0.27-1.01), respectively (Ptrend = .03). The corresponding HR (95% CI) for all-cause mortality was 0.83 (95% CI, 0.76-0.90), 0.63 (95% CI, 0.56-0.70) and 0.56 (95% CI, 0.48-0.65), respectively (Ptrend < .0001). In the joint analysis of pre- and postpolypectomy periods, patients with a healthy postpolypectomy lifestyle had a lower incidence of CRC regardless of their prepolypectomy exposure, whereas those with a healthy lifestyle in both periods had a lower mortality than those with an unhealthy lifestyle in either period. In conclusion, adherence to a healthy lifestyle after polypectomy may confer significant benefit for CRC prevention and reduction in all-cause mortality.
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Affiliation(s)
- Liang Wang
- Center of Gastrointestinal Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Digestive Disease Center, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Markus D Knudsen
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Section for colorectal cancer screening, Cancer Registry of Norway, Oslo, Norway
- Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Norwegian PSC Research Center, Oslo University Hospital, Oslo, Norway
| | - Chun-Han Lo
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Kai Wang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Mingming He
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Georgios Polychronidis
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Study Centre of the German Surgical Society, University of Heidelberg, Heidelberg, Germany
| | - Dong Hang
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, P.R. China
| | - Xiaosheng He
- Department of Colorectal Surgery, the Six Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
| | - Rong Zhong
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Andrew T. Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Shuji Ogino
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Cancer Immunology Program, Dana-Farber Harvard Cancer Center, Boston, MA, USA
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Edward L. Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Mingyang Song
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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10
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Ugai T, Väyrynen JP, Haruki K, Akimoto N, Lau MC, Zhong R, Kishikawa J, Väyrynen SA, Zhao M, Fujiyoshi K, Dias Costa A, Borowsky J, Arima K, Guerriero JL, Fuchs CS, Zhang X, Song M, Wang M, Giannakis M, Meyerhardt JA, Nowak JA, Ogino S. Smoking and Incidence of Colorectal Cancer Subclassified by Tumor-Associated Macrophage Infiltrates. J Natl Cancer Inst 2022; 114:68-77. [PMID: 34264325 PMCID: PMC8755510 DOI: 10.1093/jnci/djab142] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/03/2021] [Accepted: 07/12/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Biological evidence indicates that smoking can influence macrophage functions and polarization, thereby promoting tumor evolution. We hypothesized that the association of smoking with colorectal cancer incidence might differ by macrophage infiltrates. METHODS Using the Nurses' Health Study and the Health Professionals Follow-up Study, we examined the association of smoking with incidence of colorectal cancer subclassified by macrophage counts. Multiplexed immunofluorescence (for CD68, CD86, IRF5, MAF, and MRC1 [CD206]) combined with digital image analysis and machine learning was used to identify overall, M1-polarized, and M2-polarized macrophages in tumor. We used inverse-probability-weighted multivariable Cox proportional hazards regression models to control for potential confounders and selection bias because of tissue data availability. All statistical tests were 2-sided. RESULTS During follow-up of 131 144 participants (3 648 370 person-years), we documented 3092 incident colorectal cancer cases, including 871 cases with available macrophage data. The association of pack-years smoked with colorectal cancer incidence differed by stromal macrophage densities (Pheterogeneity = .003). Compared with never smoking, multivariable-adjusted hazard ratios (95% confidence interval) for tumors with low macrophage densities were 1.32 (0.97 to 1.79) for 1-19 pack-years, 1.31 (0.92 to 1.85) for 20-39 pack-years, and 1.74 (1.26 to 2.41) for 40 or more pack-years (Ptrend = .004). In contrast, pack-years smoked was not statistically significantly associated with the incidence of tumors having intermediate or high macrophage densities (Ptrend > .009, with an α level of .005). No statistically significant differential association was found for colorectal cancer subclassified by M1-like or M2-like macrophages. CONCLUSIONS The association of smoking with colorectal cancer incidence is stronger for tumors with lower stromal macrophage counts. Our findings suggest an interplay of smoking and macrophages in colorectal carcinogenesis.
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Affiliation(s)
- Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Juha P Väyrynen
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Naohiko Akimoto
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Mai Chan Lau
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Rong Zhong
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Junko Kishikawa
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Sara A Väyrynen
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Melissa Zhao
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kenji Fujiyoshi
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Andressa Dias Costa
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Jennifer Borowsky
- Conjoint Gastroenterology Department, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
| | - Kota Arima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Jennifer L Guerriero
- Breast Tumor Immunology Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA
- Division of Breast Surgery, Department of Surgery, Brigham and Women’s Hospital, Boston, MA, USA
| | - Charles S Fuchs
- Yale Cancer Center, New Haven, CT, USA
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
- Smilow Cancer Hospital, New Haven, CT, USA
- Genentech, South San Francisco, CA, USA
| | - Xuehong Zhang
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Molin Wang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Jeffrey A Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Jonathan A Nowak
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA
- Correspondence to: Shuji Ogino, MD, PhD, MS, Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, 221 Longwood Ave, EBRC Rm 404A, Boston, MA 02115, USA (e-mail: )
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11
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Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol 2021; 14:101174. [PMID: 34243011 PMCID: PMC8273208 DOI: 10.1016/j.tranon.2021.101174] [Citation(s) in RCA: 1263] [Impact Index Per Article: 315.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 07/01/2021] [Accepted: 07/02/2021] [Indexed: 02/07/2023] Open
Abstract
As the third most common malignancy and the second most deadly cancer, colorectal cancer (CRC) induces estimated 1.9 million incidence cases and 0.9 million deaths worldwide in 2020. The incidence of CRC is higher in highly developed countries, and it is increasing in middle- and low-income countries due to westernization. Moreover, a rising incidence of early-onset CRC is also emerging. The large number of CRC cases poses a growing global public health challenge. Raising awareness of CRC is important to promote healthy lifestyle choices, novel strategies for CRC management, and implementation of global screening programs, which are critical to reducing CRC morbidity and mortality in the future. CRC is a heterogeneous disease, and its subtype affiliation influences prognosis and therapeutic response. An accurate CRC subtype classification system is of great significance for basic research and clinical outcome. Here, we present the global epidemiology of CRC in 2020 and projections for 2040, review the major CRC subtypes to better understand CRC molecular basis, and summarize current risk factors, prevention, and screening strategies for CRC.
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Affiliation(s)
- Yue Xi
- Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA
| | - Pengfei Xu
- Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA.
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12
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Wang X, Amitay E, Harrison TA, Banbury BL, Berndt SI, Brenner H, Buchanan DD, Campbell PT, Cao Y, Chan AT, Chang-Claude J, Gallinger SJ, Giannakis M, Giles GG, Gunter MJ, Hopper JL, Jenkins MA, Lin Y, Moreno V, Nishihara R, Newcomb PA, Ogino S, Phipps AI, Sakoda LC, Schoen RE, Slattery ML, Song M, Sun W, Thibodeau SN, Toland AE, Van Guelpen B, Woods MO, Hsu L, Hoffmeister M, Peters U. Association Between Smoking and Molecular Subtypes of Colorectal Cancer. JNCI Cancer Spectr 2021; 5:pkab056. [PMID: 34377935 PMCID: PMC8346704 DOI: 10.1093/jncics/pkab056] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 03/25/2021] [Accepted: 04/30/2021] [Indexed: 12/24/2022] Open
Abstract
Background Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking. Methods A total of 9789 CRC cases and 11 231 controls of European ancestry from 11 observational studies were included. We harmonized smoking variables across studies and derived sex study-specific quartiles of pack-years of smoking for analysis. Four somatic colorectal tumor markers were assessed individually and in combination, including BRAF mutation, KRAS mutation, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status. A multinomial logistic regression analysis was used to assess the association between smoking and risk of CRC subtypes by molecular characteristics, adjusting for age, sex, and study. All statistical tests were 2-sided and adjusted for Bonferroni correction. Results Heavier smoking was associated with higher risk of CRC overall and stratified by individual markers (P trend < .001). The associations differed statistically significantly between all molecular subtypes, which was the most statistically significant for CIMP and BRAF. Compared with never-smokers, smokers in the fourth quartile of pack-years had a 90% higher risk of CIMP-positive CRC (odds ratio = 1.90, 95% confidence interval = 1.60 to 2.26) but only 35% higher risk for CIMP-negative CRC (odds ratio = 1.35, 95% confidence interval = 1.22 to 1.49; P difference = 2.1 x 10-6). The association was also stronger in tumors that were CIMP positive, MSI high, or KRAS wild type when combined (P difference < .001). Conclusion Smoking was associated with differential risk of CRC subtypes defined by molecular characteristics. Heavier smokers had particularly higher risk of CRC subtypes that were CIMP positive and MSI high in combination, suggesting that smoking may be involved in the development of colorectal tumors via the serrated pathway.
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Affiliation(s)
- Xiaoliang Wang
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Efrat Amitay
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Tabitha A Harrison
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Barbara L Banbury
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Sonja I Berndt
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Department of Preventive Oncology, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Daniel D Buchanan
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia
- Department of Clinical Pathology, Colorectal Oncogenomics Group, The University of Melbourne, Parkville, Victoria, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia
- Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Peter T Campbell
- Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO, USA
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA
- Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
- Genetic Tumour Epidemiology Group, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Steven J Gallinger
- Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Graham G Giles
- Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, Australia
- Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
| | - Marc J Gunter
- Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - John L Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia
| | - Mark A Jenkins
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia
| | - Yi Lin
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Victor Moreno
- Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain
| | - Reiko Nishihara
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Polly A Newcomb
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Shuji Ogino
- Department of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Amanda I Phipps
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Lori C Sakoda
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Robert E Schoen
- Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Martha L Slattery
- Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, USA
| | - Mingyang Song
- Division of Gastroenterology, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA
| | - Wei Sun
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Steven N Thibodeau
- Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Amanda E Toland
- Departments of Cancer Biology and Genetics and Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Bethany Van Guelpen
- Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden
| | - Michael O Woods
- Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland & Labrador, Canada
| | - Li Hsu
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Ulrike Peters
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
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13
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Dai J, Nishi A, Tran N, Yamamoto Y, Dewey G, Ugai T, Ogino S. Revisiting social MPE: an integration of molecular pathological epidemiology and social science in the new era of precision medicine. Expert Rev Mol Diagn 2021; 21:869-886. [PMID: 34253130 DOI: 10.1080/14737159.2021.1952073] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Molecular pathological epidemiology (MPE) is an integrative transdisciplinary area examining the relationships between various exposures and pathogenic signatures of diseases. In line with the accelerating advancements in MPE, social science and its health-related interdisciplinary areas have also developed rapidly. Accumulating evidence indicates the pathological role of social-demographic factors. We therefore initially proposed social MPE in 2015, which aims to elucidate etiological roles of social-demographic factors and address health inequalities globally. With the ubiquity of molecular diagnosis, there are ample opportunities for researchers to utilize and develop the social MPE framework. AREAS COVERED Molecular subtypes of breast cancer have been investigated rigorously for understanding its etiologies rooted from social factors. Emerging evidence indicates pathogenic heterogeneity of neurological disorders such as Alzheimer's disease. Presenting specific patterns of social-demographic factors across different molecular subtypes should be promising for advancing the screening, prevention, and treatment strategies of those heterogeneous diseases. This article rigorously reviewed literatures investigating differences of race/ethnicity and socioeconomic status across molecular subtypes of breast cancer and Alzheimer's disease to date. EXPERT OPINION With advancements of the multi-omics technologies, we foresee a blooming of social MPE studies, which can address health disparities, advance personalized molecular medicine, and enhance public health.
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Affiliation(s)
- Jin Dai
- Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, United States
| | - Akihiro Nishi
- Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, United States.,California Center for Population Research, University of California, Los Angeles, CA United States
| | - Nathan Tran
- Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, United States
| | - Yasumasa Yamamoto
- Graduate School of Advanced Integrated Studies in Human Survivability, Kyoto University, Sakyo-ku, Kyoto Japan
| | - George Dewey
- Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, United States
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States.,Cancer Immunology Program, Dana-Farber Harvard Cancer Center, Boston, Massachusetts, United States.,Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, United States
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14
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Association between risk factors, molecular features and CpG island methylator phenotype colorectal cancer among different age groups in a Taiwanese cohort. Br J Cancer 2021; 125:48-54. [PMID: 33846524 DOI: 10.1038/s41416-021-01300-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 01/27/2021] [Accepted: 02/03/2021] [Indexed: 12/09/2022] Open
Abstract
BACKGROUND CpG island methylator phenotype (CIMP) represents a carcinogenesis pathway of colorectal cancer (CRC) and the association between CIMP CRC, molecular features and risk factors in East Asian population is less studied. METHODS We prospectively enrolled newly diagnosed CRC patients at the National Taiwan University Hospital. Clinicopathological data and risk factors for CRC were collected during interview. The tumour samples were subjected to CIMP, RAS/BRAF mutation and microsatellite instability tests. CIMP-high was determined when ≧3 methylated loci of p16, MINT1, MINT2, MINT31 and MLH1 were identified. Multivariate logistic regression was used to evaluate the association between risk factors and CIMP-high CRC. RESULTS Compared with CIMP-low/negative CRC, CIMP-high CRC was associated with more stage IV disease, BRAF V600E mutation and high body mass index (BMI ≧ 27.5 kg/m2) in younger patients (age < 50 y), and more right-sided tumour, BRAF V600E mutation, MSI-high and colorectal polyp in elder patients (age ≧ 50 y). Multivariate analyses showed that BMI ≧27.5 kg/m2 was significantly associated with CIMP-high CRC in younger patients. CONCLUSIONS We identified distinct clinicopathological features for CIMP-high CRC among different age groups in Taiwan. Our data suggest the association between BMI ≧27.5 kg/m2 and CIMP-high CRC in patients younger than 50 years.
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15
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Mo S, Wang H, Han L, Xiang W, Dai W, Zhao P, Pei F, Su Z, Ma C, Li Q, Wang Z, Cai S, Wang H, Liu R, Cai G. Fecal Multidimensional Assay for Non-Invasive Detection of Colorectal Cancer: Fecal Immunochemical Test, Stool DNA Mutation, Methylation, and Intestinal Bacteria Analysis. Front Oncol 2021; 11:643136. [PMID: 33718241 PMCID: PMC7947614 DOI: 10.3389/fonc.2021.643136] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 01/15/2021] [Indexed: 12/15/2022] Open
Abstract
Background Fecal immunochemical test (FIT), DNA mutation, DNA methylation, and microbial dysbiosis all showed promising in colorectal cancer (CRC) non-invasive detection. We assessed CRC detection with an assay combining all these strategies and investigated the effect of clinical features on the performance of this comprehensive test. Methods We performed a multidimensional analysis study using stool samples collected from 108 patients with CRC, 18 patients with colorectal adenoma, and 36 individuals with no evidence of colorectal disease. The multidimensional analysis of stool samples including FIT, stool DNA (sDNA) tests for three methylated genes (Septin9, NDRG4, BMP3) and three mutated genes (KRAS, BRAF, PI3KCA) using next generation sequencing as well as detection of stool bacteria level of Fusobacterium nucleatum and Parvimonas micra using qPCR method. We used a linear support vector classification model to analyze the data. Results The sensitivity of FIT alone was 69.4% for CRC and 11.1% for adenoma. Separately, the sensitivity of the detection of intestinal bacteria, DNA mutation, and DNA methylation for CRC was 58.3, 50.0, and 51.9%, respectively. The combination of FIT and sDNA tests had a sensitivity of 81.5% for CRC (AUC: 0.93, better than FIT alone, P = 0.017) and 27.8% for adenoma with 94.4% specificity. Sensitivity of the multidimensional test to detect CRC with stage II (84.6%) and III (91.9%) CRC was relatively higher (88.2%) than that of patients with stage I (60.0%) and stage IV (75.0%) (P = 0.024). The rate of CRC detection increased with tumor size (P = 0.008) and age (P = 0.04). Interestingly, the rate of CRC detection was higher in smoking persons than non-smokers with marginal significance (P = 0.08). Conclusions The multidimensional assay of stool samples combining FIT and stool DNA tests further improved the diagnostic sensitivity for CRC. This could provide new approach for improvement of CRC screening and further demonstrations are warranted.
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Affiliation(s)
- Shaobo Mo
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Hui Wang
- Department of Research and Development, Singlera Genomics (Shanghai) Ltd., Shanghai, China
| | - Lingyu Han
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wenqiang Xiang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Weixing Dai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Pengfei Zhao
- Department of Research and Development, Singlera Genomics (Shanghai) Ltd., Shanghai, China
| | - Fengchun Pei
- Department of Research and Development, Singlera Genomics (Shanghai) Ltd., Shanghai, China
| | - Zhixi Su
- Department of Research and Development, Singlera Genomics (Shanghai) Ltd., Shanghai, China
| | - Chengcheng Ma
- Department of Research and Development, Singlera Genomics (Shanghai) Ltd., Shanghai, China
| | - Qi Li
- Department of Medical Oncology and Cancer Institute, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhimin Wang
- Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center, Shanghai Industrial Technology Institute, Shanghai, China
| | - Sanjun Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
| | - Hao Wang
- Department of Colorectal Surgery, Chang Hai Hospital, Naval Medical University, Shanghai, China
| | - Rui Liu
- Department of Research and Development, Singlera Genomics (Shanghai) Ltd., Shanghai, China
| | - Guoxiang Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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16
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Wang L, He X, Ugai T, Haruki K, Lo CH, Hang D, Akimoto N, Fujiyoshi K, Wang M, Fuchs CS, Meyerhardt JA, Zhang X, Wu K, Chan AT, Giovannucci EL, Ogino S, Song M. Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes. JNCI Cancer Spectr 2021; 5:pkaa089. [PMID: 33442661 PMCID: PMC7791624 DOI: 10.1093/jncics/pkaa089] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 08/28/2020] [Accepted: 09/09/2020] [Indexed: 12/27/2022] Open
Abstract
Background Colorectal cancer (CRC) is a heterogeneous disease that can develop via 3 major pathways: conventional, serrated, and alternate. We aimed to examine whether the risk factor profiles differ according to pathway-related molecular subtypes. Methods We examined the association of 24 risk factors with 4 CRC molecular subtypes based on a combinatorial status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations by collecting data from 2 large US cohorts. We used inverse probability weighted duplication-method Cox proportional hazards regression to evaluate differential associations across subtypes. Results We documented 1175 CRC patients with molecular subtype data: subtype 1 (n = 498; conventional pathway; non-MSI-high, CIMP-low or negative, BRAF-wild-type, KRAS-wild-type), subtype 2 (n = 138; serrated pathway; any MSI status, CIMP-high, BRAF-mutated, KRAS-wild-type), subtype 3 (n = 367; alternate pathway; non-MSI-high, CIMP-low or negative, BRAF-wild-type, KRAS-mutated), and subtype 4 (n = 172; other marker combinations). Statistically significant heterogeneity in associations with CRC subtypes was found for age, sex, and smoking, with a higher hazard ratio (HR) observed for the subtype 2 (HR per 10 years of age = 2.64, 95% CI = 2.13 to 3.26; HR for female = 2.65, 95% CI = 1.60 to 4.39; HR per 20-pack-year of smoking = 1.29, 95% CI = 1.14 to 1.45) than other CRC subtypes (all P heterogeneity < .005). A stronger association was found for adiposity measures with subtype 1 CRC in men and subtype 3 CRC in women and for several dietary factors with subtype 1 CRC, although these differences did not achieve statistical significance at α level of .005. Conclusions Risk factor profiles may differ for CRC arising from different molecular pathways.
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Affiliation(s)
- Liang Wang
- Center of Gastrointestinal Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P.R. China
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Xiaosheng He
- Department of Colorectal Surgery, the Six Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
| | - Tomotaka Ugai
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Program in MPE Molecular Pathological Epidemiology, Boston, MA, USA
| | - Koichiro Haruki
- Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Program in MPE Molecular Pathological Epidemiology, Boston, MA, USA
| | - Chun-Han Lo
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Dong Hang
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, P.R. China
| | - Naohiko Akimoto
- Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Program in MPE Molecular Pathological Epidemiology, Boston, MA, USA
| | - Kenji Fujiyoshi
- Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Program in MPE Molecular Pathological Epidemiology, Boston, MA, USA
| | - Molin Wang
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Charles S Fuchs
- Department of Medicine, Yale Cancer Center, New Haven, CT, USA
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
- Department of Medicine, Smilow Cancer Hospital, New Haven, CT, USA
| | - Jeffrey A Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Kana Wu
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Shuji Ogino
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Program in MPE Molecular Pathological Epidemiology, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA
| | - Mingyang Song
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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17
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The microbiome, genetics, and gastrointestinal neoplasms: the evolving field of molecular pathological epidemiology to analyze the tumor-immune-microbiome interaction. Hum Genet 2020; 140:725-746. [PMID: 33180176 DOI: 10.1007/s00439-020-02235-2] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 10/23/2020] [Indexed: 02/06/2023]
Abstract
Metagenomic studies using next-generation sequencing technologies have revealed rich human intestinal microbiome, which likely influence host immunity and health conditions including cancer. Evidence indicates a biological link between altered microbiome and cancers in the digestive system. Escherichia coli and Bacteroides fragilis have been found to be enriched in colorectal mucosal tissues from patients with familial adenomatous polyposis that is caused by germline APC mutations. In addition, recent studies have found enrichment of certain oral bacteria, viruses, and fungi in tumor tissue and fecal specimens from patients with gastrointestinal cancer. An integrative approach is required to elucidate the role of microorganisms in the pathogenic process of gastrointestinal cancers, which develop through the accumulation of somatic genetic and epigenetic alterations in neoplastic cells, influenced by host genetic variations, immunity, microbiome, and environmental exposures. The transdisciplinary field of molecular pathological epidemiology (MPE) offers research frameworks to link germline genetics and environmental factors (including diet, lifestyle, and pharmacological factors) to pathologic phenotypes. The integration of microbiology into the MPE model (microbiology-MPE) can contribute to better understanding of the interactive role of environment, tumor cells, immune cells, and microbiome in various diseases. We review major clinical and experimental studies on the microbiome, and describe emerging evidence from the microbiology-MPE research in gastrointestinal cancers. Together with basic experimental research, this new research paradigm can help us to develop new prevention and treatment strategies for gastrointestinal cancers through targeting of the microbiome.
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18
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Fujiyoshi K, Chen Y, Haruki K, Ugai T, Kishikawa J, Hamada T, Liu L, Arima K, Borowsky J, Väyrynen JP, Zhao M, Lau MC, Gu S, Shi S, Akimoto N, Twombly TS, Drew DA, Song M, Chan AT, Giovannucci EL, Meyerhardt JA, Fuchs CS, Nishihara R, Lennerz JK, Giannakis M, Nowak JA, Zhang X, Wu K, Ogino S. Smoking Status at Diagnosis and Colorectal Cancer Prognosis According to Tumor Lymphocytic Reaction. JNCI Cancer Spectr 2020; 4:pkaa040. [PMID: 32923934 PMCID: PMC7477375 DOI: 10.1093/jncics/pkaa040] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 03/30/2020] [Accepted: 05/06/2020] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Smoking has been associated with worse colorectal cancer patient survival and may potentially suppress the immune response in the tumor microenvironment. We hypothesized that the prognostic association of smoking behavior at colorectal cancer diagnosis might differ by lymphocytic reaction patterns in cancer tissue. METHODS Using 1474 colon and rectal cancer patients within 2 large prospective cohort studies (Nurses' Health Study and Health Professionals Follow-up Study), we characterized 4 patterns of histopathologic lymphocytic reaction, including tumor-infiltrating lymphocytes (TILs), intratumoral periglandular reaction, peritumoral lymphocytic reaction, and Crohn's-like lymphoid reaction. Using covariate data of 4420 incident colorectal cancer patients in total, an inverse probability weighted multivariable Cox proportional hazards regression model was conducted to adjust for selection bias due to tissue availability and potential confounders, including tumor differentiation, disease stage, microsatellite instability status, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. RESULTS The prognostic association of smoking status at diagnosis differed by TIL status. Compared with never smokers, the multivariable-adjusted colorectal cancer-specific mortality hazard ratio for current smokers was 1.50 (95% confidence interval = 1.10 to 2.06) in tumors with negative or low TIL and 0.43 (95% confidence interval = 0.16 to 1.12) in tumors with intermediate or high TIL (2-sided P interaction = .009). No statistically significant interactions were observed in the other patterns of lymphocytic reaction. CONCLUSIONS The association of smoking status at diagnosis with colorectal cancer mortality may be stronger for carcinomas with negative or low TIL, suggesting a potential interplay of smoking and lymphocytic reaction in the colorectal cancer microenvironment.
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Affiliation(s)
- Kenji Fujiyoshi
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Surgery, Kurume University, Kurume, Fukuoka, Japan
| | - Yang Chen
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Junko Kishikawa
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Tsuyoshi Hamada
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Li Liu
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Kota Arima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Jennifer Borowsky
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Juha P Väyrynen
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Melissa Zhao
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Mai Chan Lau
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Simeng Gu
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Shanshan Shi
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Naohiko Akimoto
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Tyler S Twombly
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - David A Drew
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Mingyang Song
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Edward L Giovannucci
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Jeffrey A Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Charles S Fuchs
- Yale Cancer Center, New Haven, CT, USA
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
- Smilow Cancer Hospital, New Haven, CT, USA
| | - Reiko Nishihara
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Jochen K Lennerz
- Department of Pathology, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA
| | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Jonathan A Nowak
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA
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19
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Wang L, Lo CH, He X, Hang D, Wang M, Wu K, Chan AT, Ogino S, Giovannucci EL, Song M. Risk Factor Profiles Differ for Cancers of Different Regions of the Colorectum. Gastroenterology 2020; 159:241-256.e13. [PMID: 32247020 PMCID: PMC7387153 DOI: 10.1053/j.gastro.2020.03.054] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 03/11/2020] [Accepted: 03/23/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS The molecular features of colorectal tumors differ with their anatomic location. Colorectal tumors are usually classified as proximal or distal. We collected data from 3 cohorts to identify demographic, clinical, anthropometric, lifestyle, and dietary risk factors for colorectal cancer (CRC) at 7 anatomic subsites. We examined whether the associations differ among refined subsites and whether there are trends in associations from cecum to rectum. METHODS We collected data from the Nurses' Health Study, Nurses' Health Study 2, and Health Professionals Follow-up Study (45,351 men and 178,016 women, followed for a median 23 years) on 24 risk factors in relation to risk of cancer in cecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectosigmoid junction, and rectum. Hazard ratios were estimated using Cox proportional hazards regression. We tested for linear and nonlinear trends in associations with CRC among subsites and within proximal colon, distal colon, and rectum. RESULTS We documented 3058 cases of CRC (474 in cecum, 633 in ascending colon, 250 in transverse colon, 221 in descending colon, 750 in sigmoid colon, 202 in rectosigmoid junction, and 528 in rectum). The positive associations with cancer risk decreased, from cecum to rectum, for age and family history of CRC. In contrast, the inverse associations with cancer risk increased, from cecum to rectum, for endoscopic screening and intake of whole grains, cereal fiber, and processed red meat. There was a significant nonlinear trend in the association between CRC and female sex, with hazard ratios ranging from 1.73 for ascending colon cancer to 0.54 for sigmoid colon cancer. For proximal colon cancers, the association with alcohol consumption and smoking before age 30 years increased from the cecum to transverse colon. For distal colon cancers, the positive association with waist circumference in men was greater for descending vs sigmoid colon cancer. CONCLUSIONS In an analysis of 3058 cases of CRC, we found that risk factor profiles differed for cancers along the colorectum. Proximal vs distal classifications are not sufficient to encompass the regional variations in colorectal tumor features and risk factors.
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Affiliation(s)
- Liang Wang
- Center of Gastrointestinal Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Chun-Han Lo
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Xiaosheng He
- Department of Colorectal Surgery, the Six Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
| | - Dong Hang
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, P.R. China
| | - Molin Wang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Shuji Ogino
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Mingyang Song
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
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20
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Jung YS, Kim NH, Lee MY, Park JH, Park DI, Sohn CI. Effect of Cotinine-Verified Change in Smoking Status on Risk of Metachronous Colorectal Neoplasia After Polypectomy. Clin Gastroenterol Hepatol 2020; 18:163-170. [PMID: 30772586 DOI: 10.1016/j.cgh.2019.02.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 02/07/2019] [Accepted: 02/10/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Previous assessments of colorectal neoplasia (CRN) recurrence after polypectomy used self-report to determine smoking status. We evaluated the association between change in smoking status and metachronous CRN risk after polypectomy using cotinine level in urine to determine tobacco exposure. METHODS We performed a retrospective study of participants in the Kangbuk Samsung Health Study in Korea who underwent a screening colonoscopy examination and measurement of cotinine in urine samples. Our analysis included 4762 patients who had 1 or more adenomas detected in an index colonoscopy performed between January 2010 and December 2014, and underwent a surveillance colonoscopy, 6 or more months later, until December 2017. RESULTS Patients were classified into 4 groups based on the change in cotinine-verified smoking status from index to follow-up colonoscopy (mean interval, 3.2 ± 1.3 y), as follows: remained nonsmokers (n = 2962; group 1), smokers changed to nonsmokers (n = 600; group 2), nonsmokers changed to smokers (n = 138; group 3), and remained smokers (n = 1062; group 4). After adjustment for confounding factors, group 4 had a significantly higher risk of metachronous CRN than group 1 (hazard ratio [HR], 1.54; 95% CI, 1.36-1.73) and group 2 (HR, 1.63; 95% CI, 1.39-1.99). Group 4 also had a higher risk of metachronous advanced CRN than group 1 (HR, 2.84; 95% CI, 1.79-4.53) and group 2 (HR, 2.10; 95% CI, 1.13-3.89). Group 3 had a higher risk of metachronous CRN than group 1 (HR, 1.50; 95% CI, 1.14-1.97) and group 2 (HR, 1.62; 95% CI, 1.20-2.20). CONCLUSIONS In a retrospective study of individuals with at least 1 adenoma, we found that cotinine-verified changes in smoking status between index and follow-up colonoscopy are associated with a risk of metachronous CRN. Helping patients quit smoking is important for effective prevention of colorectal cancer.
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Affiliation(s)
- Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Nam Hee Kim
- Preventive Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Mi Yeon Lee
- Division of Biostatistics, Department of R&D Management, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Chong Il Sohn
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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21
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Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol 2019; 16:713-732. [PMID: 31455888 DOI: 10.1038/s41575-019-0189-8] [Citation(s) in RCA: 1518] [Impact Index Per Article: 253.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/11/2019] [Indexed: 02/06/2023]
Abstract
Globally, colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer death. Arising through three major pathways, including adenoma-carcinoma sequence, serrated pathway and inflammatory pathway, CRC represents an aetiologically heterogeneous disease according to subtyping by tumour anatomical location or global molecular alterations. Genetic factors such as germline MLH1 and APC mutations have an aetiologic role, predisposing individuals to CRC. Yet, the majority of CRC is sporadic and largely attributable to the constellation of modifiable environmental risk factors characterizing westernization (for example, obesity, physical inactivity, poor diets, alcohol drinking and smoking). As such, the burden of CRC is shifting towards low-income and middle-income countries as they become westernized. Furthermore, the rising incidence of CRC at younger ages (before age 50 years) is an emerging trend. This Review provides a comprehensive summary of CRC epidemiology, with emphasis on modifiable lifestyle and nutritional factors, chemoprevention and screening. Overall, the optimal reduction of CRC incidence and mortality will require concerted efforts to reduce modifiable risk factors, to leverage chemoprevention research and to promote population-wide and targeted screening.
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Affiliation(s)
- NaNa Keum
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.,Department of Food Science and Biotechnology, Dongguk University, Goyang, South Korea
| | - Edward Giovannucci
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. .,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. .,Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. .,Department of Medicine, Harvard Medical School, Boston, MA, USA.
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22
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Carr PR, Alwers E, Bienert S, Weberpals J, Kloor M, Brenner H, Hoffmeister M. Lifestyle factors and risk of sporadic colorectal cancer by microsatellite instability status: a systematic review and meta-analyses. Ann Oncol 2019; 29:825-834. [PMID: 29438474 DOI: 10.1093/annonc/mdy059] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Introduction The association of lifestyle factors with molecular pathological subtypes of colorectal cancer (CRC), such as microsatellite instability (MSI), could provide further knowledge about the colorectal carcinogenic process. The aim of this review was to evaluate possible associations between lifestyle factors and risk of sporadic CRC by MSI status. Methods PubMed and Web of Science were searched for studies investigating the association between alcohol, body mass index, dietary fiber, hormone replacement therapy (HRT), non-steroidal anti-inflammatory drugs, physical activity, red meat, smoking, or statin use, with MSI-high (MSI-H) and microsatellite stable (MSS) CRC. Meta-analyses were carried out to calculate summary relative risks (sRR). Results Overall, 31 studies reporting on the association between lifestyle factors and CRC according to MSI status were included in this review. Ever smoking was associated with MSI-H (sRR = 1.62; 95% CI: 1.40-1.88) and MSS/MSI-low CRC (sRR = 1.10; 95% CI: 1.01-1.20), but the association was significantly stronger for MSI-H CRC. The use of HRT was associated with a 20% decrease (sRR = 0.80; 95% CI: 0.73-0.89) in the risk of MSS CRC, but was not associated with MSI-H CRC. An increase in body mass index per 5 kg/m2 was equally associated with MSS and MSI-H CRC (sRR = 1.22, in both cases), but was statistically significant for MSS CRC only (95% CI: 1.11-1.34 and 0.94-1.58, respectively). Limited evidence for associations between other lifestyle factors and CRC by MSI status exists. Conclusions Lifestyle factors, such as HRT and smoking are differentially associated with the risk of MSI-H and MSS CRC. Further research on associations of lifestyle factors and CRC subtypes is necessary to provide a better understanding of the CRC disease pathway.
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Affiliation(s)
- P R Carr
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - E Alwers
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - S Bienert
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - J Weberpals
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - M Kloor
- Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany
| | - H Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - M Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
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23
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Advani SM, Advani PS, Brown DW, DeSantis SM, Korphaisarn K, VonVille HM, Bressler J, Lopez DS, Davis JS, Daniel CR, Sarshekeh AM, Braithwaite D, Swartz MD, Kopetz S. Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer. BMC Cancer 2019; 19:964. [PMID: 31623592 PMCID: PMC6796359 DOI: 10.1186/s12885-019-6144-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 09/10/2019] [Indexed: 02/07/2023] Open
Abstract
Background CpG Island Methylator Phenotype (CIMP) is an epigenetic phenotype in CRC characterized by hypermethylation of CpG islands in promoter regions of tumor suppressor genes, leading to their transcriptional silencing and loss of function. While the prevalence of CRC differs across geographical regions, no studies have compared prevalence of CIMP-High phenotype across regions. The purpose of this project was to compare the prevalence of CIMP across geographical regions after adjusting for variations in methodologies to measure CIMP in a meta-analysis. Methods We searched PubMed, Medline, and Embase for articles focusing on CIMP published from 2000 to 2018. Two reviewers independently identified 111 articles to be included in final meta-analysis. We classified methods used to quantify CIMP into 4 categories: a) Classical (MINT marker) Panel group b) Weisenberg-Ogino (W-O) group c) Human Methylation Arrays group and d) Miscellaneous group. We compared the prevalence of CIMP across geographical regions after correcting for methodological variations using meta-regression techniques. Results The pooled prevalence of CIMP-High across all studies was 22% (95% confidence interval:21–24%; I2 = 94.75%). Pooled prevalence of CIMP-H across Asia, Australia, Europe, North America and South America was 22, 21, 21, 27 and 25%, respectively. Meta-regression analysis identified no significant differences in the prevalence of CIMP-H across geographical regions after correction for methodological variations. In exploratory analysis, we observed variations in CIMP-H prevalence across countries. Conclusion Although no differences were found for CIMP-H prevalence across countries, further studies are needed to compare the influence of demographic, lifestyle and environmental factors in relation to the prevalence of CIMP across geographical regions.
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Affiliation(s)
- Shailesh Mahesh Advani
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0426, Houston, TX, 77030, USA. .,Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, 20007, USA. .,Social Behavioral Research Branch, National Human Genome Research Institute, National Institute of Health, Bethesda, MD, 20892, USA.
| | - Pragati Shailesh Advani
- Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Institutes of Health, National Cancer Institute, Rockville, MD, 20850, USA
| | - Derek W Brown
- Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Stacia M DeSantis
- Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Krittiya Korphaisarn
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0426, Houston, TX, 77030, USA
| | - Helena M VonVille
- Library, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Jan Bressler
- Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - David S Lopez
- Division of Urology- UTHealth McGovern Medical School, Houston, TX, 77030, USA.,Department of Preventive Medicine and Community Health, UTMB Health-School of Medicine, Galveston, TX, 77555-1153, USA
| | - Jennifer S Davis
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Carrie R Daniel
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Amir Mehrvarz Sarshekeh
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0426, Houston, TX, 77030, USA
| | - Dejana Braithwaite
- Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, 20007, USA
| | - Michael D Swartz
- Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0426, Houston, TX, 77030, USA.
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24
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Lima Passos V, Crutzen R, Feder JT, Willemsen MC, Lemmens P, Hummel K. Dynamic, data-driven typologies of long-term smoking, cessation, and their correlates: Findings from the International Tobacco Control (ITC) Netherlands Survey. Soc Sci Med 2019; 235:112393. [PMID: 31302376 DOI: 10.1016/j.socscimed.2019.112393] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Revised: 05/24/2019] [Accepted: 06/29/2019] [Indexed: 01/04/2023]
Abstract
RATIONALE Efforts towards tobacco control are numerous, but relapse rates for smoking cessations remain high. Behavioral changes necessary for continuous cessation appear complex, variable and subject to social, biological, psychological and environmental determinants. Currently, most cessation studies concentrate on short-to midterm behavioral changes. Besides, they use fixed typologies, thereby failing to capture the temporal changes in smoking/cessation behaviors, and its determinants. OBJECTIVE To obtain long-term, data-driven longitudinal patterns or profiles of smoking, cessation, and related determinants in a cohort of adult smokers, and to investigate their dynamic links. METHODS The dataset originated from the International Tobacco Control (ITC) Netherlands Project, waves 2008 to 2016. Temporal dynamics of smoking/cessation, psychosocial constructs, and time-varying determinants of smoking were extracted with Group-Based Trajectory Modeling technique. Their associations were investigated via multiple regression models. RESULTS Substantial heterogeneity of smoking and cessation behaviors was unveiled. Most respondents were classified as persistent smokers, albeit with distinct levels of consumption. For a minority, cessation could be sustained between 1 and 8 years, while others showed relapsing or fluctuating smoking behavior. Links between smoking/cessation trajectories with those of psychosocial and sociodemographic variables were diverse. Notably, changes in two variables were aligned to behavioral changes towards cessation: decreasing number of smoking peers and attaining a higher self-perceived control. CONCLUSION The unveiled heterogeneity of smoking behavior over time and the varied cross-dependencies between smoking data-driven typologies and those of underlying risk factors underscore the need of individually tailored approaches for motivational quitting.
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Affiliation(s)
- Valéria Lima Passos
- Department of Methodology and Statistics, Maastricht University, CAPHRI Care and Public Health Research Institute, Peter Debyeplein, 1, 6229, HA, Maastricht, the Netherlands.
| | - Rik Crutzen
- Department of Health Promotion, CAPHRI Care and Public Health Research Institute, Maastricht University, P.O. Box 616, 6200, MD, Maastricht, the Netherlands.
| | - Johannes T Feder
- Department of Methodology and Statistics, Maastricht University, CAPHRI Care and Public Health Research Institute, Peter Debyeplein, 1, 6229, HA, Maastricht, the Netherlands.
| | - Marc C Willemsen
- Department of Health Promotion, CAPHRI Care and Public Health Research Institute, Maastricht University, P. Debyeplein 1, 6229, HA, Maastricht, the Netherlands.
| | - Paul Lemmens
- Department of Health Promotion, CAPHRI Care and Public Health Research Institute, Maastricht University, P. Debyeplein 1, 6229, HA, Maastricht, the Netherlands.
| | - Karin Hummel
- Department of Health Promotion, CAPHRI Care and Public Health Research Institute, Maastricht University, P.O. Box 616, 6200, MD, Maastricht, the Netherlands.
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25
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Crockett SD. Don't Smoke 'em if You Got 'em: Tobacco Exposure Increases Risk of Serrated Polyps. Clin Gastroenterol Hepatol 2019; 17:1441-1443. [PMID: 30743008 DOI: 10.1016/j.cgh.2019.02.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 02/05/2019] [Indexed: 02/07/2023]
Affiliation(s)
- Seth D Crockett
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
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26
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Williams LA, Yang JJ, Hirsch BA, Marcotte EL, Spector LG. Is There Etiologic Heterogeneity between Subtypes of Childhood Acute Lymphoblastic Leukemia? A Review of Variation in Risk by Subtype. Cancer Epidemiol Biomarkers Prev 2019; 28:846-856. [PMID: 30770347 PMCID: PMC6500468 DOI: 10.1158/1055-9965.epi-18-0801] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 09/19/2018] [Accepted: 02/05/2019] [Indexed: 02/07/2023] Open
Abstract
Although substantial advances in the identification of cytogenomic subtypes of childhood acute lymphoblastic leukemia (ALL) have been made in recent decades, epidemiologic research characterizing the etiologic heterogeneity of ALL by subtype has not kept pace. The purpose of this review is to summarize the current literature concerning subtype-specific epidemiologic risk factor associations with ALL subtype defined by immunophenotype (e.g., B-cell vs. T-cell) and cytogenomics (including gross chromosomal events characterized by recurring numerical and structural abnormalities, along with cryptic balanced rearrangements, and focal gene deletions). In case-control analyses investigating nongenetic risk factors, home paint exposure is associated with hyperdiploid, MLL-rearranged, and ETV6-RUNX1 subtypes, yet there are few differences in risk factor associations between T- and B-ALL. Although the association between maternal smoking and ALL overall has been null, maternal smoking is associated with an increasing number of gene deletions among cases. GWAS-identified variants in ARID5B have been the most extensively studied and are strongly associated with hyperdiploid B-ALL. GATA3 single nucleotide variant rs3824662 shows a strong association with Ph-like ALL (OR = 3.14). However, there have been relatively few population-based studies of adequate sample size to uncover risk factors that may define etiologic heterogeneity between and within the currently defined cytogenomic ALL subtypes.
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Affiliation(s)
- Lindsay A Williams
- Division of Epidemiology & Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
| | - Jun J Yang
- Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee
- Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
| | - Betsy A Hirsch
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota
- Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
| | - Erin L Marcotte
- Division of Epidemiology & Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
- Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
| | - Logan G Spector
- Division of Epidemiology & Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
- Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
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27
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Liu PH, Lebwohl B, Burke KE, Ivey KL, Ananthakrishnan AN, Lochhead P, Olen O, Ludvigsson JF, Richter JM, Chan AT, Khalili H. Dietary Gluten Intake and Risk of Microscopic Colitis Among US Women without Celiac Disease: A Prospective Cohort Study. Am J Gastroenterol 2019; 114:127-134. [PMID: 30181535 PMCID: PMC6329641 DOI: 10.1038/s41395-018-0267-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Microscopic colitis is a common cause of chronic watery diarrhea among the elderly. Although the prevalence of celiac disease appears to be higher in patients with microscopic colitis, the relationship between dietary gluten intake and risk of microscopic colitis among individuals without celiac disease has not been explored. METHODS We conducted a prospective study of 160,744 US women without celiac disease enrolled in the Nurses' Health Study (NHS) and the NHSII. Dietary gluten intake was estimated using validated food frequency questionnaires every 4 years. Microscopic colitis was confirmed through medical records review. We used Cox proportional hazard modeling to estimate the multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI). RESULTS We documented 219 incident cases of microscopic colitis over more than 20 years of follow-up encompassing 3,716,718 person-years (crude incidence rate: 5.9/100,000 person-years) in NHS and NHSII. Dietary gluten intake was not associated with risk of microscopic colitis (Ptrend = 0.88). Compared to individuals in the lowest quintile of energy-adjusted gluten intake, the adjusted HR of microscopic colitis was 1.18 (95% CI: 0.77-1.78) for the middle quintile and 1.03 (95% CI: 0.67-1.58) for the highest quintile. Additional adjustment for primary dietary sources of gluten including refined and whole grains did not materially alter the effect estimates (All Ptrend ≥ 0.69). The null association did not differ according to lymphocytic or collagenous subtypes (Pheterogeneity = 0.72) and was not modified by age, smoking status, or body mass index (All Pinteraction ≥ 0.17). CONCLUSIONS Dietary gluten intake during adulthood was not associated with risk of microscopic colitis among women without celiac disease.
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Affiliation(s)
- Po-Hong Liu
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Benjamin Lebwohl
- Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Kristin E. Burke
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Kerry L. Ivey
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- South Australian Health and Medical Research Institute, Infection and Immunity Theme, School of Medicine, Flinders University, Adelaide, Australia
| | - Ashwin N. Ananthakrishnan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Paul Lochhead
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Ola Olen
- Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
| | - Jonas F. Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden
| | - James M. Richter
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew T. Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Hamed Khalili
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
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28
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Hamada T, Nowak JA, Masugi Y, Drew DA, Song M, Cao Y, Kosumi K, Mima K, Twombly TS, Liu L, Shi Y, da Silva A, Gu M, Li W, Nosho K, Keum N, Giannakis M, Meyerhardt JA, Wu K, Wang M, Chan AT, Giovannucci EL, Fuchs CS, Nishihara R, Zhang X, Ogino S. Smoking and Risk of Colorectal Cancer Sub-Classified by Tumor-Infiltrating T Cells. J Natl Cancer Inst 2019; 111:42-51. [PMID: 30312431 PMCID: PMC6335108 DOI: 10.1093/jnci/djy137] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 07/10/2018] [Indexed: 02/06/2023] Open
Abstract
Background Evidence indicates not only carcinogenic effect of cigarette smoking but also its immunosuppressive effect. We hypothesized that the association of smoking with colorectal cancer risk might be stronger for tumors with lower anti-tumor adaptive immune response. Methods During follow-up of 134 981 participants (3 490 851 person-years) in the Nurses' Health Study and Health Professionals Follow-up Study, we documented 729 rectal and colon cancer cases with available data on T-cell densities in tumor microenvironment. Using the duplication-method Cox regression model, we examined a differential association of smoking status with risk of colorectal carcinoma subclassified by densities of CD3+ cells, CD8+ cells, CD45RO (PTPRC)+ cells, or FOXP3+ cells. All statistical tests were two-sided. Results The association of smoking status with colorectal cancer risk differed by CD3+ cell density (Pheterogeneity = .007). Compared with never smokers, multivariable-adjusted hazard ratios for CD3+ cell-low colorectal cancer were 1.38 (95% confidence interval = 1.09 to 1.75) in former smokers and 1.59 (95% confidence interval = 1.14 to 2.23) in current smokers (Ptrend = .002, across smoking status categories). In contrast, smoking status was not associated with CD3+ cell-high cancer risk (Ptrend = .52). This differential association appeared consistent in strata of microsatellite instability, CpG island methylator phenotype, or BRAF mutation status. There was no statistically significant differential association according to densities of CD8+ cells, CD45RO+ cells, or FOXP3+ cells (Pheterogeneity > .04, with adjusted α of 0.01). Conclusions Colorectal cancer risk increased by smoking was stronger for tumors with lower T-lymphocyte response, suggesting an interplay of smoking and immunity in colorectal carcinogenesis.
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Affiliation(s)
| | - Jonathan A Nowak
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
- Program in Molecular Pathological Epidemiology, Department of Pathology
| | | | - David A Drew
- Clinical and Translational Epidemiology Unit, and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Mingyang Song
- Clinical and Translational Epidemiology Unit, and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
- Department of Nutrition
| | - Yin Cao
- Clinical and Translational Epidemiology Unit, and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
- Department of Nutrition
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO
| | | | - Kosuke Mima
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
| | | | - Li Liu
- Department of Oncologic Pathology
- Department of Nutrition
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO
- Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Hubei, P.R. China
| | - Yan Shi
- Department of Oncologic Pathology
- Department of Medical Oncology, Chinese PLA General Hospital, Beijing, P.R. China
| | | | - Mancang Gu
- Department of Oncologic Pathology
- College of Pharmacy, Zhejiang Chinese Medical University, Zhejiang, P.R. China
| | | | - Katsuhiko Nosho
- Department of Gastroenterology, Rheumatology, and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - NaNa Keum
- Department of Nutrition
- Department of Food Science and Biotechnology, Dongguk University, Goyang, the Republic of Korea
| | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
- Department of Medicine, and Channing Division of Network Medicine
- Broad Institute of MIT and Harvard, Cambridge, MA
| | | | - Kana Wu
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
- Department of Nutrition
- Department of Epidemiology
| | - Molin Wang
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
- Department of Epidemiology
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Andrew T Chan
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
- Clinical and Translational Epidemiology Unit, and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Edward L Giovannucci
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
- Department of Nutrition
- Department of Epidemiology
| | - Charles S Fuchs
- Yale Cancer Center, New Haven, CT
- Department of Medicine, Yale School of Medicine, New Haven, CT
- Smilow Cancer Hospital, New Haven, CT
| | - Reiko Nishihara
- Department of Oncologic Pathology
- Program in Molecular Pathological Epidemiology, Department of Pathology
- Department of Nutrition
- Department of Epidemiology
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Xuehong Zhang
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Shuji Ogino
- Department of Oncologic Pathology
- Program in Molecular Pathological Epidemiology, Department of Pathology
- Department of Epidemiology
- Broad Institute of MIT and Harvard, Cambridge, MA
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Deng W, Lu YF. Methylation of tumor suppressor genes and risk factors of colorectal cancer. Shijie Huaren Xiaohua Zazhi 2018; 26:2088-2095. [DOI: 10.11569/wcjd.v26.i36.2088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Although the diagnostic methods and treatment options are continuously optimized, the incidence and mortality of colorectal cancer (CRC) are still rising. Therefore, "preventive treatment of disease" is the key to solving this problem. In recent years, hypermethylation of promoter CpG islands (CGIs) in tumor suppressor genes has been a hot research topic because it is reversible and early events in the development of CRC, and affects drug resistance, disease treatment, and patient prognosis. CRC risk factors such as poor dietary choice, lack of physical activity, excessive drinking, and unhealthy weight can regulate promoter CGI hypermethylation, which will help develop new methylation-related cancer prevention strategies. This article mainly introduces the significance and regulatory mechanism of methylation of tumor suppressor genes and its relationship with risk factors in CRC.
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Affiliation(s)
- Wei Deng
- Department of Gastroenterology, the Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
| | - Yong-Fu Lu
- Department of Gastroenterology, the Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
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Smoking Habits are Strongly Associated With Colorectal Polyps in a Population-based Case-control Study. J Clin Gastroenterol 2018; 52:805-811. [PMID: 29210901 DOI: 10.1097/mcg.0000000000000935] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
GOALS The goal of this study is to test the association between lifetime smoking habits and colorectal polyps of different classifications. BACKGROUND Smoking is an established risk factor for several cancers, including colorectal cancer. However, the association between lifetime smoking habits including intensity, duration, and cessation, and premalignant colorectal polyps is yet to be established. STUDY A case-control study among 828 consecutive subjects aged 40 to 70 years, undergoing screening or diagnostic colonoscopy. Exclusion criteria were: medically treated diabetes, colectomy, and belonging to colorectal cancer high risk group. Polyps were stratified according to histology (serrated or adenomatous polyp) and location. All participants underwent anthropometric measurements and a structured medical and lifestyle interview. RESULTS Current-smoking was more strongly associated with increased odds for distal rather than proximal polyps [odds ratio (OR), 4.00; 95% confidence interval (CI), 2.40-6.68 and OR, 2.52; 95% CI, 1.46-4.36, respectively], with serrated-polyps rather than adenomas (OR, 6.36; 95% CI, 2.77-14.57 and OR, 3.01; 1.90-4.74, respectively). All levels of smoking intensity (daily cigarettes) were associated with colorectal polyps. A dose-response association was seen between smoking duration and colorectal polyps. Smoking duration of ≥20 years was strongly associated with distal polyps (OR, 4.01; 95% CI, 1.62-9.84), independently of potential confounders, smoking intensity and years since smoking cessation. All associations were stronger for distal serrated polyps. CONCLUSIONS Smoking duration is associated with colorectal plyps, independently of other potential confounders, smoking intensity, and cessation. The association is stronger with distal rather than proximal polyps, and with serrated polyps rather than adenomas.
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Ogino S, Nowak JA, Hamada T, Phipps AI, Peters U, Milner DA, Giovannucci EL, Nishihara R, Giannakis M, Garrett WS, Song M. Integrative analysis of exogenous, endogenous, tumour and immune factors for precision medicine. Gut 2018; 67:1168-1180. [PMID: 29437869 PMCID: PMC5943183 DOI: 10.1136/gutjnl-2017-315537] [Citation(s) in RCA: 128] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 01/02/2018] [Accepted: 01/05/2018] [Indexed: 12/14/2022]
Abstract
Immunotherapy strategies targeting immune checkpoints such as the CTLA4 and CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) T-cell coreceptor pathways are revolutionising oncology. The approval of pembrolizumab use for solid tumours with high-level microsatellite instability or mismatch repair deficiency by the US Food and Drug Administration highlights promise of precision immuno-oncology. However, despite evidence indicating influences of exogenous and endogenous factors such as diet, nutrients, alcohol, smoking, obesity, lifestyle, environmental exposures and microbiome on tumour-immune interactions, integrative analyses of those factors and immunity lag behind. Immune cell analyses in the tumour microenvironment have not adequately been integrated into large-scale studies. Addressing this gap, the transdisciplinary field of molecular pathological epidemiology (MPE) offers research frameworks to integrate tumour immunology into population health sciences, and link the exposures and germline genetics (eg, HLA genotypes) to tumour and immune characteristics. Multilevel research using bioinformatics, in vivo pathology and omics (genomics, epigenomics, transcriptomics, proteomics and metabolomics) technologies is possible with use of tissue, peripheral blood circulating cells, cell-free plasma, stool, sputum, urine and other body fluids. This immunology-MPE model can synergise with experimental immunology, microbiology and systems biology. GI neoplasms represent exemplary diseases for the immunology-MPE model, given rich microbiota and immune tissues of intestines, and the well-established carcinogenic role of intestinal inflammation. Proof-of-principle studies on colorectal cancer provided insights into immunomodulating effects of aspirin, vitamin D, inflammatory diets and omega-3 polyunsaturated fatty acids. The integrated immunology-MPE model can contribute to better understanding of environment-tumour-immune interactions, and effective immunoprevention and immunotherapy strategies for precision medicine.
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Affiliation(s)
- Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA,Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA,Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA
| | - Jonathan A Nowak
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Tsuyoshi Hamada
- Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Amanda I Phipps
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA,Department of Epidemiology, University of Washington, Seattle, Washington, USA
| | - Ulrike Peters
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA,Department of Epidemiology, University of Washington, Seattle, Washington, USA
| | - Danny A Milner
- American Society for Clinical Pathology, Chicago, Illinois, USA
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA,Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Reiko Nishihara
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA,Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA,Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Marios Giannakis
- Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA,Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA,Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Wendy S Garrett
- Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA,Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA,Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA,Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Mandal P. Molecular mechanistic pathway of colorectal carcinogenesis associated with intestinal microbiota. Anaerobe 2018; 49:63-70. [DOI: 10.1016/j.anaerobe.2017.12.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Revised: 09/24/2017] [Accepted: 12/18/2017] [Indexed: 12/13/2022]
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Lifestyle, Diet, and Colorectal Cancer Risk According to (Epi)genetic Instability: Current Evidence and Future Directions of Molecular Pathological Epidemiology. CURRENT COLORECTAL CANCER REPORTS 2017; 13:455-469. [PMID: 29249914 PMCID: PMC5725509 DOI: 10.1007/s11888-017-0395-0] [Citation(s) in RCA: 86] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Purpose of Review In this review, we describe molecular pathological epidemiology (MPE) studies from around the world that have studied diet and/or lifestyle factors in relation to molecular markers of (epi)genetic pathways in colorectal cancer (CRC), and explore future perspectives in this realm of research. The main focus of this review is diet and lifestyle factors for which there is evidence for an association with CRC as identified by the World Cancer Research Fund reports. In addition, we review promising hypotheses, that warrant consideration in future studies. Recent Findings Associations between molecular characteristics of CRC have been published in relation to smoking, alcohol consumption; body mass index (BMI); waist:hip ratio; adult attained height; physical activity; early life energy restriction; dietary acrylamide, fiber, fat, methyl donors, omega 3 fatty acids; meat, including total protein, processed meat, and heme iron; and fruit and vegetable intake. Summary MPE studies help identify where associations between diet, lifestyle, and CRC risk may otherwise be masked and also shed light on how timing of exposure can influence etiology. Sample size is often an issue, but this may be addressed in the future by pooling data.
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Liu PH, Cao Y, Keeley BR, Tam I, Wu K, Strate LL, Giovannucci EL, Chan AT. Adherence to a Healthy Lifestyle is Associated With a Lower Risk of Diverticulitis among Men. Am J Gastroenterol 2017; 112:1868-1876. [PMID: 29112202 PMCID: PMC5736501 DOI: 10.1038/ajg.2017.398] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 09/01/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Diverticulitis is a common disease with high clinical burden. We evaluated the joint contribution of multiple lifestyle factors to risks of incident diverticulitis. We also estimated the proportion of diverticulitis preventable by lifestyle modifications. METHODS We prospectively examined the association between lifestyle factors (red meat, dietary fiber intake, vigorous physical activity (activity with metabolic equivalent ≥6), body mass index (BMI), and smoking) and risk of diverticulitis among participants in the Health Professionals Follow-Up Study. RESULTS We documented 907 incident cases of diverticulitis during 757,791 person-years. High intake of red meat, low intake of dietary fiber, low vigorous physical activity, high BMI, and smoking were independently associated with increased risks of diverticulitis (all P<0.05). Low-risk lifestyle was defined as average red meat intake <51 g per day, dietary fiber intake in the top 40% of the cohort (about 23 g per day), vigorous physical activity in the highest 50% among participants with non-zero vigorous physical activity (roughly 2 h of exercise weekly), normal BMI between 18.5-24.9 kg m-2, and never-smoker. There was an inverse linear relationship between number of low-risk lifestyle factors and diverticulitis incidence (P for trend<0.001). Compared with men with no low-risk lifestyle factors, the multivariable relative risks of diverticulitis were 0.71 (95% confidence interval (CI): 0.59-0.87) for men with 1 low-risk lifestyle factor; 0.66 (95% CI: 0.55-0.81) for 2 low-risk factors; 0.50 (95% CI: 0.40-0.62) for 3 low-risk factors; 0.47 (95% CI: 0.35-0.62) for 4 low-risk factors, and 0.27 (95% CI: 0.15-0.48) for 5 low-risk factors. Adherence to a low-risk lifestyle could prevent 50% (95% CI: 20-71%) of incident diverticulitis. CONCLUSIONS Adherence to a low-risk lifestyle is associated with reduced incidence of diverticulitis.
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Affiliation(s)
- Po-Hong Liu
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114
| | - Yin Cao
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114,Department of Nutrition, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115,Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, 660S. Euclid Avenue, St. Louis, MO 63110
| | - Brieze R. Keeley
- Department of Medicine, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114
| | - Idy Tam
- Tufts University School of Medicine, Boston, MA, 02111
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115
| | - Lisa L. Strate
- Division of Gastroenterology, University of Washington School of Medicine, Harborview Medical Center, 325 Ninth Ave, Box 359773, Seattle, WA 98104
| | - Edward L. Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115,Department of Nutrition, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115,Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 181 Longwood Ave, Boston, MA 02115
| | - Andrew T. Chan
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114,Broad Institute of MIT and Harvard, Cambridge, MA 02139
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Barrow TM, Klett H, Toth R, Böhm J, Gigic B, Habermann N, Scherer D, Schrotz-King P, Skender S, Abbenhardt-Martin C, Zielske L, Schneider M, Ulrich A, Schirmacher P, Herpel E, Brenner H, Busch H, Boerries M, Ulrich CM, Michels KB. Smoking is associated with hypermethylation of the APC 1A promoter in colorectal cancer: the ColoCare Study. J Pathol 2017; 243:366-375. [PMID: 28791728 DOI: 10.1002/path.4955] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 07/02/2017] [Accepted: 08/01/2017] [Indexed: 12/22/2022]
Abstract
Smoking tobacco is a known risk factor for the development of colorectal cancer and for mortality associated with the disease. Smoking has been reported to be associated with changes in DNA methylation in blood and in lung tumour tissues, although there has been scant investigation of how epigenetic factors may be implicated in the increased risk of developing colorectal cancer. To identify epigenetic changes associated with smoking behaviours, we performed epigenome-wide analysis of DNA methylation in colorectal tumours from 36 never-smokers, 47 former smokers, and 13 active smokers, and in adjacent mucosa from 49 never-smokers, 64 former smokers, and 18 active smokers. Our analyses identified 15 CpG sites within the APC 1A promoter that were significantly hypermethylated and 14 CpG loci within the NFATC1 gene body that were significantly hypomethylated (pLIS < 1 × 10-5 ) in the tumours of active smokers. The APC 1A promoter was hypermethylated in 7 of 36 tumours from never-smokers (19%), 12 of 47 tumours from former smokers (26%), and 8 of 13 tumours from active smokers (62%). Promoter hypermethylation was positively associated with duration of smoking (Spearman rank correlation, ρ = 0.26, p = 0.03) and was confined to tumours, with hypermethylation never being observed in adjacent mucosa. Further analysis of adjacent mucosa revealed significant hypomethylation of four loci associated with the TNXB gene in tissue from active smokers. Our findings provide exploratory evidence for hypermethylation of the key tumour suppressor gene APC being implicated in smoking-associated colorectal carcinogenesis. Further work is required to establish the validity of our observations in independent cohorts. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Affiliation(s)
- Timothy M Barrow
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hagen Klett
- German Cancer Consortium (DKTK), Heidelberg, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany.,Institute of Molecular Medicine and Cell Research, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Reka Toth
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jürgen Böhm
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Biljana Gigic
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Surgical Oncology, University Clinic Heidelberg, Heidelberg, Germany
| | - Nina Habermann
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Dominique Scherer
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Petra Schrotz-King
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Stephanie Skender
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Clare Abbenhardt-Martin
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Lin Zielske
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Martin Schneider
- Department of Surgical Oncology, University Clinic Heidelberg, Heidelberg, Germany
| | - Alexis Ulrich
- Department of Surgical Oncology, University Clinic Heidelberg, Heidelberg, Germany
| | - Peter Schirmacher
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Department of General Pathology, University Clinic Heidelberg, Heidelberg, Germany
| | - Esther Herpel
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Department of General Pathology, University Clinic Heidelberg, Heidelberg, Germany
| | - Hermann Brenner
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hauke Busch
- Institute of Molecular Medicine and Cell Research, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.,Lübeck Institute of Experimental Dermatology and Institute of Cardiogenetics, University of Lübeck, Lübeck, Germany
| | - Melanie Boerries
- German Cancer Consortium (DKTK), Heidelberg, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany.,Institute of Molecular Medicine and Cell Research, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Cornelia M Ulrich
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Population Sciences, Huntsman Cancer Institute, Salt Lake City, Utah, USA
| | - Karin B Michels
- German Cancer Consortium (DKTK), Heidelberg, Germany.,Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.,Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, USA
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Abstract
Decades of studies have shown that epigenetic alterations play a significant role on cancer development both in vitro and in vivo. However, considering that many cancers harbor mutations at epigenetic modifier genes and that transcription factor-mediated gene regulations are tightly coupled with epigenetic modifications, the majority of epigenetic alterations in cancers could be the consequence of the dysfunction or dysregulation of epigenetic modifiers caused by genetic abnormalities. Therefore, it remains unclear whether bona fide epigenetic abnormalities have causal roles on cancer development. Reprogramming technologies enable us to actively alter epigenetic regulations while preserving genomic information. Taking advantage, recent studies have provided in vivo evidence for the significant impact of epigenetic abnormalities on the initiation, maintenance and progression of cancer cells.
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Affiliation(s)
- Kenji Ito
- Center for iPS Cell Research & Application, Kyoto University, Kyoto 606-8507, Japan
| | - Yasuhiro Yamada
- Center for iPS Cell Research & Application, Kyoto University, Kyoto 606-8507, Japan
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Hamada T, Keum N, Nishihara R, Ogino S. Molecular pathological epidemiology: new developing frontiers of big data science to study etiologies and pathogenesis. J Gastroenterol 2017; 52:265-275. [PMID: 27738762 PMCID: PMC5325774 DOI: 10.1007/s00535-016-1272-3] [Citation(s) in RCA: 83] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Accepted: 09/22/2016] [Indexed: 02/07/2023]
Abstract
Molecular pathological epidemiology (MPE) is an integrative field that utilizes molecular pathology to incorporate interpersonal heterogeneity of a disease process into epidemiology. In each individual, the development and progression of a disease are determined by a unique combination of exogenous and endogenous factors, resulting in different molecular and pathological subtypes of the disease. Based on "the unique disease principle," the primary aim of MPE is to uncover an interactive relationship between a specific environmental exposure and disease subtypes in determining disease incidence and mortality. This MPE approach can provide etiologic and pathogenic insights, potentially contributing to precision medicine for personalized prevention and treatment. Although breast, prostate, lung, and colorectal cancers have been among the most commonly studied diseases, the MPE approach can be used to study any disease. In addition to molecular features, host immune status and microbiome profile likely affect a disease process, and thus serve as informative biomarkers. As such, further integration of several disciplines into MPE has been achieved (e.g., pharmaco-MPE, immuno-MPE, and microbial MPE), to provide novel insights into underlying etiologic mechanisms. With the advent of high-throughput sequencing technologies, available genomic and epigenomic data have expanded dramatically. The MPE approach can also provide a specific risk estimate for each disease subgroup, thereby enhancing the impact of genome-wide association studies on public health. In this article, we present recent progress of MPE, and discuss the importance of accounting for the disease heterogeneity in the era of big-data health science and precision medicine.
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Affiliation(s)
- Tsuyoshi Hamada
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave., Room SM1036, Boston, MA, 02215, USA
| | - NaNa Keum
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Reiko Nishihara
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave., Room SM1036, Boston, MA, 02215, USA.
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| | - Shuji Ogino
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave., Room SM1036, Boston, MA, 02215, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 450 Brookline Ave., Room SM1036, Boston, MA, 02215, USA.
- Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
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A Prospective Study of Smoking and Risk of Synchronous Colorectal Cancers. Am J Gastroenterol 2017; 112:493-501. [PMID: 28117362 PMCID: PMC5342916 DOI: 10.1038/ajg.2016.589] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 12/06/2016] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Cigarette smoking has been linked to somatic genetic and epigenetic aberrations, including CpG island methylator phenotype (CIMP)-high, microsatellite instability (MSI)-high and BRAF mutation. These molecular features have been associated with synchronous primary colorectal cancers (CRCs). Thus, we examined the hypothesis that smoking might be associated with the risk of synchronous CRCs. METHODS Within the Health Professionals Follow-up Study and Nurses' Health Study, we examined the relationship of smoking and incidence of CRC according to tumor synchronicity, using duplication-method Cox proportional hazards regression analysis. RESULTS We confirmed 1,981 solitary CRC and 45 synchronous CRC cases during follow-up of 134,305 individuals. CRC risk associated with smoking differed significantly by tumor synchronicity status (Pheterogeneity<0.001). When comparing current smokers with never smokers, multivariable hazard ratios (HR) were 5.27 (95% confidence interval (CI), 2.08-13.40) for synchronous CRCs and 0.97 (95% CI, 0.83-1.14) for solitary CRC. Similarly, differential associations were observed when examining cumulative pack-years smoked (Pheterogeneity=0.006). Smoking cessation for ≥10 years relative to current smoking might reduce the risk of synchronous CRCs (multivariable HR=0.42; 95% CI, 0.19-0.95), but not solitary CRC (multivariable HR=1.10; 95% CI, 0.94-1.29; Pheterogeneity=0.001). Comparing current and former smokers with never smokers, multivariable HRs for synchronous CRCs were significantly higher than those of solitary CRC positive for either CIMP-high, MSI-high, or BRAF mutation (Pheterogeneity=0.002). CONCLUSIONS Smoking is associated with an elevated risk of synchronous CRCs. Our data support a model where smoking contributes to an etiologic field effect that favors these somatic molecular alterations and the development of multiple primary tumors.
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Burón Pust A, Alison R, Blanks R, Pirie K, Gaitskell K, Barnes I, Gathani T, Reeves G, Beral V, Green J, Million Women Study Collaborators. Heterogeneity of colorectal cancer risk by tumour characteristics: Large prospective study of UK women. Int J Cancer 2017; 140:1082-1090. [PMID: 27859268 PMCID: PMC5347941 DOI: 10.1002/ijc.30527] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Revised: 11/01/2016] [Accepted: 11/08/2016] [Indexed: 12/17/2022]
Abstract
Associations between behavioural and other personal factors and colorectal cancer risk have been reported to vary by tumour characteristics, but evidence is inconsistent. In a large UK-based prospective study we examined associations of 14 postulated risk factors with colorectal cancer risk overall, and across three anatomical sites and four morphological subtypes. Among 1.3 million women, 18,518 incident colorectal cancers were identified during 13.8 (SD 3.4) years follow-up via record linkage to national cancer registry data. Cox regression yielded adjusted relative risks. Statistical significance was assessed using correction for multiple testing. Overall, colorectal cancer risk was significantly associated with height, body mass index (BMI), smoking, alcohol intake, physical activity, parity and menopausal hormone therapy use. For smoking there was substantial heterogeneity across morphological types; relative risks around two or greater were seen in current smokers both for signet ring cell and for neuroendocrine tumours. Obese women were also at higher risk for signet ring cell tumours. For adenocarcinomas, the large majority of colorectal cancers in the cohort, all risk factor associations were weak. There was little or no heterogeneity in risk between tumours of the right colon, left colon and rectum for any of the 14 factors examined. These epidemiological findings complement an emerging picture from molecular studies of possible different developmental pathways for different tumour types.
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Affiliation(s)
- Andrea Burón Pust
- Nuffield Department of Population HealthCancer Epidemiology Unit, University of OxfordUnited Kingdom
- Epidemiology and Evaluation DepartmentHospital del MarBarcelonaSpain
- IMIM (Hospital del Mar Medical Research Institute)BarcelonaSpain
- REDISSEC, Health Services Research on Chronic Patients NetworkMadridSpain
| | - Rupert Alison
- Nuffield Department of Population HealthCancer Epidemiology Unit, University of OxfordUnited Kingdom
| | - Roger Blanks
- Nuffield Department of Population HealthCancer Epidemiology Unit, University of OxfordUnited Kingdom
| | - Kirstin Pirie
- Nuffield Department of Population HealthCancer Epidemiology Unit, University of OxfordUnited Kingdom
| | - Kezia Gaitskell
- Nuffield Department of Population HealthCancer Epidemiology Unit, University of OxfordUnited Kingdom
| | - Isobel Barnes
- Nuffield Department of Population HealthCancer Epidemiology Unit, University of OxfordUnited Kingdom
| | - Toral Gathani
- Nuffield Department of Population HealthCancer Epidemiology Unit, University of OxfordUnited Kingdom
| | - Gillian Reeves
- Nuffield Department of Population HealthCancer Epidemiology Unit, University of OxfordUnited Kingdom
| | - Valerie Beral
- Nuffield Department of Population HealthCancer Epidemiology Unit, University of OxfordUnited Kingdom
| | - Jane Green
- Nuffield Department of Population HealthCancer Epidemiology Unit, University of OxfordUnited Kingdom
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Hamada T, Nishihara R, Ogino S. Post-colonoscopy colorectal cancer: the key role of molecular pathological epidemiology. Transl Gastroenterol Hepatol 2017; 2:9. [PMID: 28275741 DOI: 10.21037/tgh.2017.01.05] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 12/06/2016] [Indexed: 12/26/2022] Open
Affiliation(s)
- Tsuyoshi Hamada
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Reiko Nishihara
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; ; Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; ; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA;; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA;; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Shuji Ogino
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; ; Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; ; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA;; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
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Campbell PT, Rebbeck TR, Nishihara R, Beck AH, Begg CB, Bogdanov AA, Cao Y, Coleman HG, Freeman GJ, Heng YJ, Huttenhower C, Irizarry RA, Kip NS, Michor F, Nevo D, Peters U, Phipps AI, Poole EM, Qian ZR, Quackenbush J, Robins H, Rogan PK, Slattery ML, Smith-Warner SA, Song M, VanderWeele TJ, Xia D, Zabor EC, Zhang X, Wang M, Ogino S. Proceedings of the third international molecular pathological epidemiology (MPE) meeting. Cancer Causes Control 2017; 28:167-176. [PMID: 28097472 PMCID: PMC5303153 DOI: 10.1007/s10552-016-0845-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Accepted: 12/20/2016] [Indexed: 02/07/2023]
Abstract
Molecular pathological epidemiology (MPE) is a transdisciplinary and relatively new scientific discipline that integrates theory, methods, and resources from epidemiology, pathology, biostatistics, bioinformatics, and computational biology. The underlying objective of MPE research is to better understand the etiology and progression of complex and heterogeneous human diseases with the goal of informing prevention and treatment efforts in population health and clinical medicine. Although MPE research has been commonly applied to investigating breast, lung, and colorectal cancers, its methodology can be used to study most diseases. Recent successes in MPE studies include: (1) the development of new statistical methods to address etiologic heterogeneity; (2) the enhancement of causal inference; (3) the identification of previously unknown exposure-subtype disease associations; and (4) better understanding of the role of lifestyle/behavioral factors on modifying prognosis according to disease subtype. Central challenges to MPE include the relative lack of transdisciplinary experts, educational programs, and forums to discuss issues related to the advancement of the field. To address these challenges, highlight recent successes in the field, and identify new opportunities, a series of MPE meetings have been held at the Dana-Farber Cancer Institute in Boston, MA. Herein, we share the proceedings of the Third International MPE Meeting, held in May 2016 and attended by 150 scientists from 17 countries. Special topics included integration of MPE with immunology and health disparity research. This meeting series will continue to provide an impetus to foster further transdisciplinary integration of divergent scientific fields.
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Affiliation(s)
- Peter T Campbell
- Epidemiology Research Program, American Cancer Society, 250 Williams Street NW, Atlanta, GA, 30303, USA.
| | - Timothy R Rebbeck
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Reiko Nishihara
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Andrew H Beck
- Cancer Research Institute, Beth Israel Deaconess Cancer Center, Boston, MA, USA
- Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Colin B Begg
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alexei A Bogdanov
- Department of Radiology, University of Massachusetts Medical School, Worcester, MA, USA
| | - Yin Cao
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Helen G Coleman
- Epidemiology and Health Services Research Group, Centre for Public Health, Queens University Belfast, Belfast, Northern Ireland
| | - Gordon J Freeman
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Yujing J Heng
- Cancer Research Institute, Beth Israel Deaconess Cancer Center, Boston, MA, USA
- Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Curtis Huttenhower
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Microbial Systems and Communities, Genome Sequencing and Analysis Program, The Broad Institute, Cambridge, MA, USA
| | - Rafael A Irizarry
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - N Sertac Kip
- Laboratory Medicine and Pathology, Geisinger Health System, Danville, PA, USA
| | - Franziska Michor
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Daniel Nevo
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Ulrike Peters
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA
| | - Amanda I Phipps
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA
| | - Elizabeth M Poole
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Zhi Rong Qian
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - John Quackenbush
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Harlan Robins
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Peter K Rogan
- Department of Biochemistry, University of Western Ontario, London, Canada
| | | | - Stephanie A Smith-Warner
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Tyler J VanderWeele
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Daniel Xia
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
| | - Emily C Zabor
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Molin Wang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Shuji Ogino
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
- Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 450 Brookline Ave, Room SM1036, Boston, MA, 02215, USA.
- Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
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Yi W, Xiao E, Ding R, Luo P, Yang Y. High expression of fibronectin is associated with poor prognosis, cell proliferation and malignancy via the NF-κB/p53-apoptosis signaling pathway in colorectal cancer. Oncol Rep 2016; 36:3145-3153. [PMID: 27748871 PMCID: PMC5112592 DOI: 10.3892/or.2016.5177] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Accepted: 02/22/2016] [Indexed: 12/17/2022] Open
Abstract
Fibronectin is a glycoprotein of the extracellular matrix, and regulates the processes of self-renewal and cell cycle progression. This study aimed to investigate fibronectin expression in colorectal cancer (CRC) and elucidate the effects of fibronectin on CRC by using a knockdown approach. Immunohistochemistry was used to evaluate the expression of fibronectin in 107 CRC patient tissues and gene expression was detected by real-time quantitative PCR (qPCR) and western blot analysis. Based on the above findings, the association among fibronectin expression, clinicopathological features and prognosis was analyzed. Next, fibronectin expression was silenced by small-interfering RNAs (siRNAs) and the effects of fibronectin siRNA transfection on CRC cells and tumor growth in nude mice were assessed. Expression of genes in the NF-κB/p53-apoptosis signaling pathway were analyzed after fibronectin siRNA transfection both in vitro and in vivo. Based on the results, high expression of fibronectin was observed both in the CRC tissues and CRC cell lines. The expression level was positively correlated with TNM stage (P=0.0025) and distant metastasis (P=0.0013). By Kaplan-Meier analysis, the patients with low fibronectin expression had a longer survival time comparing to those with relatively high expression. Knockdown of fibronectin suppressed SW480 cell proliferation, migration and invasion. In addition, knockdown of fibronectin led to S phase cell cycle arrest. The following study showed that the NF-κB/p53-apoptosis signaling pathway in CRC was affected by fibronectin knockdown. Tumor formation was also depressed by fibronectin siRNA transfection of CRC cells. These results showed the significant role of fibronectin in CRC tissues and cell lines. Therefore, fibronectin may be regarded as a potential target for CRC treatment.
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Affiliation(s)
- Wenzhong Yi
- Medical Imaging Center, First People's Hospital of Huaihua City, Huaihua, Hunan 418000, P.R. China
| | - Enhua Xiao
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
| | - Ru Ding
- Medical Imaging Center, First People's Hospital of Huaihua City, Huaihua, Hunan 418000, P.R. China
| | - Ping Luo
- Department of Gastroenterology, First People's Hospital of Huaihua City, Huaihua, Hunan 418000, P.R. China
| | - Yi Yang
- Medical Imaging Center, First People's Hospital of Huaihua City, Huaihua, Hunan 418000, P.R. China
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Lee DH, Keum N, Giovannucci EL. Colorectal Cancer Epidemiology in the Nurses' Health Study. Am J Public Health 2016; 106:1599-607. [PMID: 27459444 DOI: 10.2105/ajph.2016.303320] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To review the contribution of the Nurses' Health Study (NHS) to identifying risk and protective factors for colorectal adenomas and colorectal cancer (CRC). METHODS We performed a narrative review of the publications using the NHS between 1976 and 2016. RESULTS Existing epidemiological studies using the NHS have reported that red and processed meat, alcohol, smoking, and obesity were associated with an increased risk of CRC, whereas folate, calcium, vitamin D, aspirin, and physical activity were associated with decreased risk of CRC. Moreover, modifiable factors, such as physical activity, vitamin D, folate, insulin and insulin-like growth factor binding protein-1, and diet quality, were identified to be associated with survival among CRC patients. In recent years, molecular pathological epidemiological studies have been actively conducted and have shown refined results by molecular subtypes of CRC. CONCLUSIONS The NHS has provided new insights into colorectal adenomas, CRC etiology, and pathogenic mechanisms. With its unique strengths, the NHS should continue to contribute to the field of CRC epidemiology and play a major role in public health.
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Affiliation(s)
- Dong Hoon Lee
- All authors are with the Departments of Nutrition and Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA. Edward L. Giovannucci is also with the Department of Medicine, Harvard Medical School, Boston
| | - NaNa Keum
- All authors are with the Departments of Nutrition and Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA. Edward L. Giovannucci is also with the Department of Medicine, Harvard Medical School, Boston
| | - Edward L Giovannucci
- All authors are with the Departments of Nutrition and Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA. Edward L. Giovannucci is also with the Department of Medicine, Harvard Medical School, Boston
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Townsend MK, Aschard H, De Vivo I, Michels KB, Kraft P. Genomics, Telomere Length, Epigenetics, and Metabolomics in the Nurses' Health Studies. Am J Public Health 2016; 106:1663-8. [PMID: 27459442 DOI: 10.2105/ajph.2016.303344] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVES To review the contribution of the Nurses' Health Study (NHS) and NHS II to genomics, epigenetics, and metabolomics research. METHODS We performed a narrative review of the publications of the NHS and NHS II between 1990 and 2016 based on biospecimens, including blood and tumor tissue, collected from participants. RESULTS The NHS has contributed to the discovery of genetic loci influencing more than 45 complex human phenotypes, including cancers, diabetes, cardiovascular disease, reproductive characteristics, and anthropometric traits. The combination of genomewide genotype data with extensive exposure and lifestyle data has enabled the evaluation of gene-environment interactions. Furthermore, data suggest that longer telomere length increases risk of cancers not related to smoking, and that modifiable factors (e.g., diet) may have an impact on telomere length. "Omics" research in the NHS continues to expand, with epigenetics and metabolomics becoming greater areas of focus. CONCLUSIONS The combination of prospective biomarker data and broad exposure information has enabled the NHS to participate in a variety of "omics" research, contributing to understanding of the epidemiology and biology of multiple complex diseases.
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Affiliation(s)
- Mary K Townsend
- Mary K. Townsend is with the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Hugues Aschard and Peter Kraft are with the Department of Epidemiology at the Harvard T. H. Chan School of Public Health, Boston. Immaculata De Vivo is with the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School and the Department of Epidemiology at the Harvard T. H. Chan School of Public Health. Karin B. Michels is with the Channing Division of Network Medicine in the Department of Medicine and the Obstetrics and Gynecology Epidemiology Center in the Department of Obstetrics, Gynecology, and Reproductive Biology at Brigham and Women's Hospital and Harvard Medical School, and the Department of Epidemiology at the Harvard T. H. Chan School of Public Health
| | - Hugues Aschard
- Mary K. Townsend is with the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Hugues Aschard and Peter Kraft are with the Department of Epidemiology at the Harvard T. H. Chan School of Public Health, Boston. Immaculata De Vivo is with the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School and the Department of Epidemiology at the Harvard T. H. Chan School of Public Health. Karin B. Michels is with the Channing Division of Network Medicine in the Department of Medicine and the Obstetrics and Gynecology Epidemiology Center in the Department of Obstetrics, Gynecology, and Reproductive Biology at Brigham and Women's Hospital and Harvard Medical School, and the Department of Epidemiology at the Harvard T. H. Chan School of Public Health
| | - Immaculata De Vivo
- Mary K. Townsend is with the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Hugues Aschard and Peter Kraft are with the Department of Epidemiology at the Harvard T. H. Chan School of Public Health, Boston. Immaculata De Vivo is with the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School and the Department of Epidemiology at the Harvard T. H. Chan School of Public Health. Karin B. Michels is with the Channing Division of Network Medicine in the Department of Medicine and the Obstetrics and Gynecology Epidemiology Center in the Department of Obstetrics, Gynecology, and Reproductive Biology at Brigham and Women's Hospital and Harvard Medical School, and the Department of Epidemiology at the Harvard T. H. Chan School of Public Health
| | - Karin B Michels
- Mary K. Townsend is with the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Hugues Aschard and Peter Kraft are with the Department of Epidemiology at the Harvard T. H. Chan School of Public Health, Boston. Immaculata De Vivo is with the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School and the Department of Epidemiology at the Harvard T. H. Chan School of Public Health. Karin B. Michels is with the Channing Division of Network Medicine in the Department of Medicine and the Obstetrics and Gynecology Epidemiology Center in the Department of Obstetrics, Gynecology, and Reproductive Biology at Brigham and Women's Hospital and Harvard Medical School, and the Department of Epidemiology at the Harvard T. H. Chan School of Public Health
| | - Peter Kraft
- Mary K. Townsend is with the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Hugues Aschard and Peter Kraft are with the Department of Epidemiology at the Harvard T. H. Chan School of Public Health, Boston. Immaculata De Vivo is with the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School and the Department of Epidemiology at the Harvard T. H. Chan School of Public Health. Karin B. Michels is with the Channing Division of Network Medicine in the Department of Medicine and the Obstetrics and Gynecology Epidemiology Center in the Department of Obstetrics, Gynecology, and Reproductive Biology at Brigham and Women's Hospital and Harvard Medical School, and the Department of Epidemiology at the Harvard T. H. Chan School of Public Health
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Tominaga K, Doyama H, Nakanishi H, Yoshida N, Takeda Y, Ota R, Tsuji K, Matsunaga K, Tsuji S, Takemura K, Yamada S, Katayanagi K, Kurumaya H. Importance of colonoscopy in patients undergoing endoscopic resection for superficial esophageal squamous cell carcinoma. Ann Gastroenterol 2016; 29:318-24. [PMID: 27366032 PMCID: PMC4923817 DOI: 10.20524/aog.2016.0025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Accepted: 02/09/2016] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The aim of the study was to clarify the frequency of colorectal neoplasm (CRN) complicating superficial esophageal squamous cell carcinoma (ESCC) and the need for colonoscopy. METHODS We retrospectively reviewed 101 patients who had undergone initial endoscopic resection (ER) for superficial ESCC. Control group participants were age- and sex-matched asymptomatic subjects screened at our hospital over the same period of time. Advanced adenoma was defined as an adenoma ≥10 mm, with villous features, or high-grade dysplasia. Advanced CRN referred to advanced adenoma or cancer. We measured the incidence of advanced CRN in superficial ESCC and controls, and we compared the characteristics of superficial ESCC patients with and without advanced CRN. RESULTS In the superficial ESCC group, advanced CRNs were found in 17 patients (16.8%). A history of smoking alone was found to be a significant risk factor of advanced CRN [odds ratio 6.02 (95% CI 1.30-27.8), P=0.005]. CONCLUSION The frequency of synchronous advanced CRN is high in superficial ESCC patients subjected to ER. Colonoscopy should be highly considered for most patients who undergo ER for superficial ESCC with a history of smoking, and is recommended even in superficial ESCC patients.
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Affiliation(s)
- Kei Tominaga
- Department of Gastroenterology (Kei Tominaga, Hisashi Doyama, Hiroyoshi Nakanishi, Naohiro Yoshida, Yasuhito Takeda, Ryosuke Ota, Kunihiro Tsuji, Kazuhiro Matsunaga, Shigetsugu Tsuji, Kenichi Takemura, Shinya Yamada)
| | - Hisashi Doyama
- Department of Gastroenterology (Kei Tominaga, Hisashi Doyama, Hiroyoshi Nakanishi, Naohiro Yoshida, Yasuhito Takeda, Ryosuke Ota, Kunihiro Tsuji, Kazuhiro Matsunaga, Shigetsugu Tsuji, Kenichi Takemura, Shinya Yamada)
| | - Hiroyoshi Nakanishi
- Department of Gastroenterology (Kei Tominaga, Hisashi Doyama, Hiroyoshi Nakanishi, Naohiro Yoshida, Yasuhito Takeda, Ryosuke Ota, Kunihiro Tsuji, Kazuhiro Matsunaga, Shigetsugu Tsuji, Kenichi Takemura, Shinya Yamada)
| | - Naohiro Yoshida
- Department of Gastroenterology (Kei Tominaga, Hisashi Doyama, Hiroyoshi Nakanishi, Naohiro Yoshida, Yasuhito Takeda, Ryosuke Ota, Kunihiro Tsuji, Kazuhiro Matsunaga, Shigetsugu Tsuji, Kenichi Takemura, Shinya Yamada)
| | - Yasuhito Takeda
- Department of Gastroenterology (Kei Tominaga, Hisashi Doyama, Hiroyoshi Nakanishi, Naohiro Yoshida, Yasuhito Takeda, Ryosuke Ota, Kunihiro Tsuji, Kazuhiro Matsunaga, Shigetsugu Tsuji, Kenichi Takemura, Shinya Yamada)
| | - Ryosuke Ota
- Department of Gastroenterology (Kei Tominaga, Hisashi Doyama, Hiroyoshi Nakanishi, Naohiro Yoshida, Yasuhito Takeda, Ryosuke Ota, Kunihiro Tsuji, Kazuhiro Matsunaga, Shigetsugu Tsuji, Kenichi Takemura, Shinya Yamada)
| | - Kunihiro Tsuji
- Department of Gastroenterology (Kei Tominaga, Hisashi Doyama, Hiroyoshi Nakanishi, Naohiro Yoshida, Yasuhito Takeda, Ryosuke Ota, Kunihiro Tsuji, Kazuhiro Matsunaga, Shigetsugu Tsuji, Kenichi Takemura, Shinya Yamada)
| | - Kazuhiro Matsunaga
- Department of Gastroenterology (Kei Tominaga, Hisashi Doyama, Hiroyoshi Nakanishi, Naohiro Yoshida, Yasuhito Takeda, Ryosuke Ota, Kunihiro Tsuji, Kazuhiro Matsunaga, Shigetsugu Tsuji, Kenichi Takemura, Shinya Yamada)
| | - Shigetsugu Tsuji
- Department of Gastroenterology (Kei Tominaga, Hisashi Doyama, Hiroyoshi Nakanishi, Naohiro Yoshida, Yasuhito Takeda, Ryosuke Ota, Kunihiro Tsuji, Kazuhiro Matsunaga, Shigetsugu Tsuji, Kenichi Takemura, Shinya Yamada)
| | - Kenichi Takemura
- Department of Gastroenterology (Kei Tominaga, Hisashi Doyama, Hiroyoshi Nakanishi, Naohiro Yoshida, Yasuhito Takeda, Ryosuke Ota, Kunihiro Tsuji, Kazuhiro Matsunaga, Shigetsugu Tsuji, Kenichi Takemura, Shinya Yamada)
| | - Shinya Yamada
- Department of Gastroenterology (Kei Tominaga, Hisashi Doyama, Hiroyoshi Nakanishi, Naohiro Yoshida, Yasuhito Takeda, Ryosuke Ota, Kunihiro Tsuji, Kazuhiro Matsunaga, Shigetsugu Tsuji, Kenichi Takemura, Shinya Yamada)
| | - Kazuyoshi Katayanagi
- Department of Diagnostic Pathology (Kazuyoshi Katayanagi, Hiroshi Kurumaya), Ishikawa Prefectural Central Hospital, Kanazawa, Japan
| | - Hiroshi Kurumaya
- Department of Diagnostic Pathology (Kazuyoshi Katayanagi, Hiroshi Kurumaya), Ishikawa Prefectural Central Hospital, Kanazawa, Japan
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Marczylo EL, Jacobs MN, Gant TW. Environmentally induced epigenetic toxicity: potential public health concerns. Crit Rev Toxicol 2016; 46:676-700. [PMID: 27278298 PMCID: PMC5030620 DOI: 10.1080/10408444.2016.1175417] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Throughout our lives, epigenetic processes shape our development and enable us to adapt to a constantly changing environment. Identifying and understanding environmentally induced epigenetic change(s) that may lead to adverse outcomes is vital for protecting public health. This review, therefore, examines the present understanding of epigenetic mechanisms involved in the mammalian life cycle, evaluates the current evidence for environmentally induced epigenetic toxicity in human cohorts and rodent models and highlights the research considerations and implications of this emerging knowledge for public health and regulatory toxicology. Many hundreds of studies have investigated such toxicity, yet relatively few have demonstrated a mechanistic association among specific environmental exposures, epigenetic changes and adverse health outcomes in human epidemiological cohorts and/or rodent models. While this small body of evidence is largely composed of exploratory in vivo high-dose range studies, it does set a precedent for the existence of environmentally induced epigenetic toxicity. Consequently, there is worldwide recognition of this phenomenon, and discussion on how to both guide further scientific research towards a greater mechanistic understanding of environmentally induced epigenetic toxicity in humans, and translate relevant research outcomes into appropriate regulatory policies for effective public health protection.
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Affiliation(s)
- Emma L Marczylo
- a Toxicology Department, CRCE, PHE, Chilton , Oxfordshire , UK
| | - Miriam N Jacobs
- a Toxicology Department, CRCE, PHE, Chilton , Oxfordshire , UK
| | - Timothy W Gant
- a Toxicology Department, CRCE, PHE, Chilton , Oxfordshire , UK
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Nishi A, Milner DA, Giovannucci EL, Nishihara R, Tan AS, Kawachi I, Ogino S. Integration of molecular pathology, epidemiology and social science for global precision medicine. Expert Rev Mol Diagn 2015; 16:11-23. [PMID: 26636627 PMCID: PMC4713314 DOI: 10.1586/14737159.2016.1115346] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science.
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Affiliation(s)
- Akihiro Nishi
- Yale Institute for Network Science, New Haven, CT, USA (AN); Department of Sociology, Yale University, New Haven, CT, USA (AN); Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (DAM, SO); Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA (DAM); Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN, SO); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (ELG); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA (RN); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA (RN, AST, SO); Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA (AST, IK)
| | - Danny A Milner
- Yale Institute for Network Science, New Haven, CT, USA (AN); Department of Sociology, Yale University, New Haven, CT, USA (AN); Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (DAM, SO); Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA (DAM); Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN, SO); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (ELG); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA (RN); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA (RN, AST, SO); Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA (AST, IK)
| | - Edward L. Giovannucci
- Yale Institute for Network Science, New Haven, CT, USA (AN); Department of Sociology, Yale University, New Haven, CT, USA (AN); Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (DAM, SO); Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA (DAM); Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN, SO); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (ELG); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA (RN); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA (RN, AST, SO); Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA (AST, IK)
| | - Reiko Nishihara
- Yale Institute for Network Science, New Haven, CT, USA (AN); Department of Sociology, Yale University, New Haven, CT, USA (AN); Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (DAM, SO); Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA (DAM); Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN, SO); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (ELG); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA (RN); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA (RN, AST, SO); Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA (AST, IK)
| | - Andy S. Tan
- Yale Institute for Network Science, New Haven, CT, USA (AN); Department of Sociology, Yale University, New Haven, CT, USA (AN); Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (DAM, SO); Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA (DAM); Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN, SO); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (ELG); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA (RN); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA (RN, AST, SO); Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA (AST, IK)
| | - Ichiro Kawachi
- Yale Institute for Network Science, New Haven, CT, USA (AN); Department of Sociology, Yale University, New Haven, CT, USA (AN); Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (DAM, SO); Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA (DAM); Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN, SO); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (ELG); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA (RN); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA (RN, AST, SO); Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA (AST, IK)
| | - Shuji Ogino
- Yale Institute for Network Science, New Haven, CT, USA (AN); Department of Sociology, Yale University, New Haven, CT, USA (AN); Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (DAM, SO); Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA (DAM); Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN, SO); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA (ELG, RN); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (ELG); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA (RN); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA (RN, AST, SO); Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA (AST, IK)
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Drew DA, Goh G, Mo A, Grady JJ, Forouhar F, Egan G, Swede H, Rosenberg DW, Stevens RG, Devers TJ. Colorectal polyp prevention by daily aspirin use is abrogated among active smokers. Cancer Causes Control 2015; 27:93-103. [DOI: 10.1007/s10552-015-0686-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2015] [Accepted: 10/17/2015] [Indexed: 01/03/2023]
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Nistal E, Fernández-Fernández N, Vivas S, Olcoz JL. Factors Determining Colorectal Cancer: The Role of the Intestinal Microbiota. Front Oncol 2015; 5:220. [PMID: 26528432 PMCID: PMC4601259 DOI: 10.3389/fonc.2015.00220] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Accepted: 09/24/2015] [Indexed: 12/26/2022] Open
Abstract
The gastrointestinal tract, in particular the colon, holds a complex community of microorganisms, which are essential for maintaining homeostasis. However, in recent years, many studies have implicated microbiota in the development of colorectal cancer (CRC), with this disease considered a major cause of death in the western world. The mechanisms underlying bacterial contribution in its development are complex and are not yet fully understood. However, there is increasing evidence showing a connection between intestinal microbiota and CRC. Intestinal microorganisms cause the onset and progression of CRC using different mechanisms, such as the induction of a chronic inflammation state, the biosynthesis of genotoxins that interfere with cell cycle regulation, the production of toxic metabolites, or heterocyclic amine activation of pro-diet carcinogenic compounds. Despite these advances, additional studies in humans and animal models will further decipher the relationship between microbiota and CRC, and aid in developing alternate therapies based on microbiota manipulation.
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Affiliation(s)
- Esther Nistal
- Instituto de Biomedicina (IBIOMED), Universidad de León , León , Spain
| | | | - Santiago Vivas
- Instituto de Biomedicina (IBIOMED), Universidad de León , León , Spain ; Gastroenterología, Hospital Universitario de León , León , Spain
| | - José Luis Olcoz
- Gastroenterología, Hospital Universitario de León , León , Spain
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