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Zhao J, Ji H, Li K, Yu G, Zhou S, Xiao Q, Dunlop M, Theodoratou E, Li X, Ding K. Decoding the genetic and environmental forces in propelling the surge of early-onset colorectal cancer. Chin Med J (Engl) 2025; 138:1163-1174. [PMID: 40251115 PMCID: PMC12091620 DOI: 10.1097/cm9.0000000000003601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Indexed: 04/20/2025] Open
Abstract
ABSTRACT Early-onset colorectal cancer (EOCRC) shows a different epidemiological trend compared to later-onset colorectal cancer, with its incidence rising in most regions and countries worldwide. However, the reasons behind this trend remain unclear. The etiology of EOCRC is complex and could involve both genetic and environmental factors. Apart from Lynch syndrome and Familial Adenomatous Polyposis, sporadic EOCRC exhibits a broad spectrum of pathogenic germline mutations, genetic polymorphisms, methylation changes, and chromosomal instability. Early-life exposures and environmental risk factors, including lifestyle and dietary risk factors, have been found to be associated with EOCRC risk. Meanwhile, specific chronic diseases, such as inflammatory bowel disease, diabetes, and metabolic syndrome, have been associated with EOCRC. Interactions between genetic and environmental risk factors in EOCRC have also been explored. Here we present findings from a narrative review of epidemiological studies on the assessment of early-life exposures, of EOCRC-specific environmental factors, and their interactions with susceptible loci. We also present results from EOCRC-specific genome-wide association studies that could be used to perform Mendelian randomization analyses to ascertain potential causal links between environmental factors and EOCRC.
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Affiliation(s)
- Jianhui Zhao
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, China
| | - Haosen Ji
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Kangning Li
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Guirong Yu
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Siyun Zhou
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Qian Xiao
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, China
| | - Malcolm Dunlop
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh EH8 9DX, United Kingdom
- Colon Cancer Genetics Group, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom
| | - Evropi Theodoratou
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh EH8 9DX, United Kingdom
- Colon Cancer Genetics Group, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom
| | - Xue Li
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, China
| | - Kefeng Ding
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, China
- Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, Hangzhou, Zhejiang 310009, China
- Zhejiang Provincial Clinical Research Center for CANCER, Hangzhou, Zhejiang 310009, China
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D S Freitas R, da Silva J. Impact of ultra-processed foods on human health: A comprehensive review of genomic instability and molecular mechanisms. Nutrition 2025; 137:112800. [PMID: 40393283 DOI: 10.1016/j.nut.2025.112800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 04/02/2025] [Accepted: 04/07/2025] [Indexed: 05/22/2025]
Abstract
In this review the nexus between genomic instability and human health is investigated, emphasizing the rising consumption of ultra-processed foods (UPFs). Introducing the NOVA food classification system, we explore the significant surge in UPF consumption over the past 3 decades and its correlation with heightened mortality rates. This exploration extends to the development of health issues such as obesity, cancer, type 2 diabetes, inflammatory bowel diseases, cardiovascular diseases, and depression. Existing evidence, including studies involving healthy adolescents and older adults, underscores a clear link between increased consumption of UPFs and heightened DNA damage. The primary objective of this review is to offer a comprehensive examination of the repercussions of elevated UPF consumption on human health. With a specific focus on unraveling the intricate relationship between these dietary choices and genomic instability, the review seeks to enhance our understanding. Through a targeted exploration of molecular pathways, the aim is to illuminate how dependence on UPFs may impact physical and mental well-being.
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Affiliation(s)
- Raquel D S Freitas
- Graduate Program in Health and Human Development, LaSalle University (UniLaSalle), Canoas, Rio Grande do Sul, Brazil; Laboratory of Genetic Toxicology, La Salle University (UniLaSalle), Canoas, Rio Grande do Sul, Brazil.
| | - Juliana da Silva
- Graduate Program in Health and Human Development, LaSalle University (UniLaSalle), Canoas, Rio Grande do Sul, Brazil; Laboratory of Genetic Toxicology, La Salle University (UniLaSalle), Canoas, Rio Grande do Sul, Brazil.
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Lai H, Sun M, Liu Y, Zhu H, Li M, Pan B, Wang Q, Yang Q, Cao X, Tian C, Lu Y, Song X, Ding G, Tian J, Yang K, Ge L. White rice consumption and risk of cardiometabolic and cancer outcomes: A systematic review and dose-response meta-analysis of prospective cohort studies. Crit Rev Food Sci Nutr 2023; 63:12476-12487. [PMID: 35852223 DOI: 10.1080/10408398.2022.2101984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
White rice is the food more than half of the world's population depends on. White rice intake can significantly increase the glycemic load of consumers and bring some adverse health effects. However, the quality of evidence implicating white rice in adverse health outcomes remains unclear. To evaluate the association between white rice consumption and the risk of cardiometabolic and cancer outcomes, a systematic review and dose-response meta-analysis of the relevant publications were performed. Twenty-three articles including 28 unique prospective cohorts with 1,527,198 participants proved eligible after a comprehensive search in four databases. For the risk of type 2 diabetes mellitus (T2DM), the pooled RR was 1.18 (16 more per 1000 persons) for comparing the highest with the lowest category of white rice intake, with moderate certainty evidence. Females presented a higher risk (23 more per 1000 persons) in subgroup analysis. And every additional 150 grams of white rice intake per day was associated with a 6% greater risk of T2DM (5 more per 1000 persons) with a linear positive trend. We found no significant associations between white rice intake and risk of cardiovascular diseases (CVD), CVD mortality, cancer, and metabolic syndrome. In conclusion, moderate certainty evidence demonstrated that white rice intake was associated with T2DM risk, with a linear positive trend. However, low to very low certainty of evidence suggested that no substantial associations were found between white rice intake and other cardiometabolic and cancer outcomes. More cohorts are needed to strength the evidence body.
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Affiliation(s)
- Honghao Lai
- Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China
| | - Mingyao Sun
- Evidence-Based Nursing Center, School of Nursing, Lanzhou University, Lanzhou, China
| | - Yafei Liu
- Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China
| | - Hongfei Zhu
- Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China
| | - Mengting Li
- Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China
| | - Bei Pan
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Qi Wang
- Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China
| | - Qiuyu Yang
- Evidence-Based Nursing Center, School of Nursing, Lanzhou University, Lanzhou, China
| | - Xiao Cao
- Evidence-Based Nursing Center, School of Nursing, Lanzhou University, Lanzhou, China
| | - Chen Tian
- Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China
| | - Yao Lu
- Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China
| | - Xuping Song
- Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China
| | - Guowu Ding
- Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China
| | - Jinhui Tian
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
- Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China
| | - Kehu Yang
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
- Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China
| | - Long Ge
- Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China
- Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China
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Deng JW, Zhou YL, Dai WX, Chen HM, Zhou CB, Zhu CQ, Ma XY, Pan SY, Cui Y, Xu J, Zhao EH, Wang M, Chen JX, Wang Z, Liu Q, Wang JL, Cai GX, Chen YX, Fang JY. Noninvasive predictive models based on lifestyle analysis and risk factors for early-onset colorectal cancer. J Gastroenterol Hepatol 2023; 38:1768-1777. [PMID: 37259282 DOI: 10.1111/jgh.16243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 05/10/2023] [Accepted: 05/18/2023] [Indexed: 06/02/2023]
Abstract
BACKGROUND Colorectal cancer (CRC) incidence has increased among patients aged <50 years. Exploring high-risk factors and screening high-risk populations may help lower early-onset CRC (EO-CRC) incidence. We developed noninvasive predictive models for EO-CRC and investigated its risk factors. METHODS This retrospective multicenter study collected information on 1756 patients (811 patients with EO-CRC and 945 healthy controls) from two medical centers in China. Sociodemographic features, clinical symptoms, medical and family history, lifestyle, and dietary factors were measured. Patients from one cohort were randomly assigned (8:2) to two groups for model establishment and internal validation, and another independent cohort was used for external validation. Multivariable logistic regression, random forest, and eXtreme Gradient Boosting (XGBoost) were performed to establish noninvasive predictive models for EO-CRC. Some variables in the model influenced EO-CRC occurrence and were further analyzed. Multivariable logistic regression analysis yielded adjusted odd ratios (ORs) and 95% confidence intervals (CIs). RESULTS All three models showed good performance, with areas under the receiver operator characteristic curves (AUCs) of 0.82, 0.84, and 0.82 in the internal and 0.78, 0.79, and 0.78 in the external validation cohorts, respectively. Consumption of sweet (OR 2.70, 95% CI 1.89-3.86, P < 0.001) and fried (OR 2.16, 95% CI 1.29-3.62, P < 0.001) foods ≥3 times per week was significantly associated with EO-CRC occurrence. CONCLUSION We established noninvasive predictive models for EO-CRC and identified multiple nongenetic risk factors, especially sweet and fried foods. The model has good performance and can help predict the occurrence of EO-CRC in the Chinese population.
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Affiliation(s)
- Jia-Wen Deng
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yi-Lu Zhou
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Wei-Xing Dai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
| | - Hui-Min Chen
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Cheng-Bei Zhou
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chun-Qi Zhu
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xin-Yue Ma
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Si-Yuan Pan
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yun Cui
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jia Xu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai, Jiao Tong University, Shanghai, China
| | - En-Hao Zhao
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai, Jiao Tong University, Shanghai, China
| | - Ming Wang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai, Jiao Tong University, Shanghai, China
| | - Jin-Xian Chen
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai, Jiao Tong University, Shanghai, China
| | - Zheng Wang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai, Jiao Tong University, Shanghai, China
| | - Qiang Liu
- Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ji-Lin Wang
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Guo-Xiang Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
| | - Ying-Xuan Chen
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jing-Yuan Fang
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Kim J, Lee J, Oh JH, Sohn DK, Shin A, Kim J, Chang HJ. Dietary methyl donor nutrients, DNA mismatch repair polymorphisms, and risk of colorectal cancer based on microsatellite instability status. Eur J Nutr 2022; 61:3051-3066. [PMID: 35353199 DOI: 10.1007/s00394-022-02833-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 02/09/2022] [Indexed: 12/31/2022]
Abstract
PURPOSE Colorectal cancer (CRC) is a heterogeneous disease caused by complex interplay among the diet, the environment, and genetics involving numerous molecules and pathological pathways. This study aimed to determine whether methyl donor nutrients are associated with CRC and how these associations are altered by DNA mismatch repair (MMR) genes. METHODS In total, 626 cases and 838 age- and sex-matched controls were recruited for this case-control study. A validated food frequency questionnaire was used to assess seven methyl donor nutrients (vitamin B2, niacin, B6, folate, B12, methionine, and choline). MMR polymorphisms were genotyped using an Illumina MEGA-Expanded Array. For the 626 patients, the microsatellite instability status and immunohistochemical expression of MMR proteins were analyzed. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Among the methyl donor nutrients, B2, niacin, B6, folate, and methionine were inversely associated with CRC risk, while a high intake of choline increased CRC. Regarding MMR genes, three hMSH3 polymorphisms (rs32952 A > C, rs41097 A > G, and rs245404 C > G) reduced CRC risk. Regarding gene-diet interactions, a stronger interaction effect was observed in G allele carriers of hMSH3 rs41097 with high niacin intake than in AA carriers with low niacin intake (OR, 95% CI = 0.49, 0.33-0.72, P for interaction = 0.02) in subgroups of patients with distal colon cancer (P for interaction = 0.008) and MMR proficiency with microsatellite stability (P for interaction = 0.021). CONCLUSIONS Methyl donor nutrients may affect CRC risk leading to a balance in the MMR machinery.
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Affiliation(s)
- Jimi Kim
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang-si, 10408, Gyeonggi-do, South Korea
| | - Jeonghee Lee
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang-si, 10408, Gyeonggi-do, South Korea
| | - Jae Hwan Oh
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang-si, 10408, Gyeonggi-do, South Korea
| | - Dae Kyung Sohn
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang-si, 10408, Gyeonggi-do, South Korea
| | - Aesun Shin
- Department of Preventive Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, 03080, Seoul, South Korea
- Cancer Research Institute, Seoul National University, 103 Daehak-ro, Jongno-gu, 03080, Seoul, South Korea
| | - Jeongseon Kim
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang-si, 10408, Gyeonggi-do, South Korea.
| | - Hee Jin Chang
- Division of Precision Medicine, Research Institute, and Department of Pathology, National Cancer Center Hospital, National Cancer Center, Goyang-si, 10408, Gyeonggi-do, South Korea.
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Chen X, Hoffmeister M, Brenner H. Red and Processed Meat Intake, Polygenic Risk Score, and Colorectal Cancer Risk. Nutrients 2022; 14:nu14051077. [PMID: 35268052 PMCID: PMC8912739 DOI: 10.3390/nu14051077] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 02/28/2022] [Accepted: 03/01/2022] [Indexed: 12/12/2022] Open
Abstract
High red and processed meat intake (RPMI) is an established risk factor for colorectal cancer (CRC). We aimed to assess the impact of RPMI on CRC risk according to and in comparison with genetically determined risk, which was quantified by a polygenic risk score (PRS). RPMI and potential confounders (ascertained by questionnaire) and a PRS (based on 140 CRC-related loci) were obtained from 5109 CRC cases and 4134 controls in a population-based case−control study. Associations of RPMI with CRC risk across PRS levels were assessed using logistic regression models and compared to effect estimates of PRS using “genetic risk equivalent” (GRE), a novel metric for effective risk communication. RPMI multiple times/week, 1 time/day, and >1 time/day was associated with 19% (95% CI 1% to 41%), 41% (18% to 70%), and 73% (30% to 132%) increased CRC risk, respectively, when compared to RPMI ≤ 1 time/week. Associations were independent of PRS levels (pinteraction = 0.97). The effect of RPMI > 1 time/day was equivalent to the effect of having 42 percentiles higher PRS level (GRE 42, 95% CI 20−65). RPMI increases CRC risk regardless of PRS levels. Avoiding RPMI can compensate for a substantial proportion of polygenic risk for CRC.
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Affiliation(s)
- Xuechen Chen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (X.C.); (M.H.)
- Medical Faculty Heidelberg, Heidelberg University, 69117 Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (X.C.); (M.H.)
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; (X.C.); (M.H.)
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120 Heidelberg, Germany
- Correspondence:
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Ibragimova S, Ramachandran R, Ali FR, Lipovich L, Ho SB. Dietary Patterns and Associated Microbiome Changes that Promote Oncogenesis. Front Cell Dev Biol 2021; 9:725821. [PMID: 34869313 PMCID: PMC8633417 DOI: 10.3389/fcell.2021.725821] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 10/25/2021] [Indexed: 12/24/2022] Open
Abstract
The recent increases in cancer incidences have been linked to lifestyle changes that result in obesity and metabolic syndrome. It is now evident that these trends are associated with the profound changes that occur in the intestinal microbiome, producing altered microbial population signatures that interact, directly or indirectly, with potentially pro-carcinogenic molecular pathways of transcription, proliferation, and inflammation. The effects of the entire gut microbial population on overall health are complex, but individual bacteria are known to play important and definable roles. Recent detailed examinations of a large number of subjects show a tight correlation between habitual diets, fecal microbiome signatures, and markers of metabolic health. Diets that score higher in healthfulness or diversity such as plant-based diets, have altered ratios of specific bacteria, including an increase in short-chain fatty acid producers, which in turn have been linked to improved metabolic markers and lowered cancer risk. Contrarily, numerous studies have implicated less healthy, lower-scoring diets such as the Western diet with reduced intestinal epithelial defenses and promotion of specific bacteria that affect carcinogenic pathways. In this review, we will describe how different dietary patterns affect microbial populations in the gut and illustrate the subsequent impact of bacterial products and metabolites on molecular pathways of cancer development, both locally in the gut and systemically in distant organs.
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Affiliation(s)
- Shakhzada Ibragimova
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, Dubai, UAE
| | - Revathy Ramachandran
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, Dubai, UAE
| | - Fahad R Ali
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, Dubai, UAE
| | - Leonard Lipovich
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, Dubai, UAE
| | - Samuel B Ho
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, Dubai, UAE.,Department of Medicine, Mediclinic City Hospital, Dubai Healthcare City, Dubai, UAE
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8
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Wu F, Wang B, Zhuang P, Lu Z, Li Y, Wang H, Liu X, Zhao X, Yang W, Jiao J, Zheng W, Zhang Y. Association of preserved vegetable consumption and prevalence of colorectal polyps: results from the Lanxi Pre-colorectal Cancer Cohort (LP3C). Eur J Nutr 2021; 61:1273-1284. [PMID: 34750639 DOI: 10.1007/s00394-021-02719-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 10/18/2021] [Indexed: 01/06/2023]
Abstract
PURPOSE Although fresh vegetable consumption has been linked with a lower risk of colorectal polyps, a precursor lesion for colorectal cancer (CRC), the association between preserved vegetable consumption and colorectal polyps is unknown. We aimed to assess the association of preserved vegetable intake with the prevalence of colorectal polyps with the consideration of subsites, sizes and multiplicity of polyps. METHODS We analyzed the cross-sectional data from 40-80 years Chinese at a high risk of CRC from the Lanxi Pre-colorectal Cancer Cohort (LP3C) baseline survey, which was conducted between March 2018 and December 2019. Dietary information was obtained via a validated food frequency questionnaire. Multivariate logistic regression was employed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of preserved vegetable consumption and the prevalence of colorectal polyps. RESULTS Of 6783 eligible participants in 2018-2019 survey of LP3C, 2064 prevalent colorectal polyp cases were identified. In the multivariable-adjusted model, preserved vegetable consumption was positively associated with the prevalence of colorectal polyps (OR for fourth vs. first quartile: 1.18; 95% CI 1.01-1.36; P trend = 0.02). The similar association was also detected for small polyps [ORQ4 vs Q1 (95% CI): 1.17 (1.00-1.37); P trend = 0.03]. The similar trend was detected for multiple polyps [OR Q4 vs Q1 (95% CI):1.27 (0.98-1.64); P trend = 0.04], proximal colon polyps [ORQ4 vs Q1 (95% CI): 1.12 (0.90-1.38); P trend = 0.07], and single polyp [ORQ4 vs Q1 (95% CI) for 1.15 (0.98-1.35); P trend = 0.06]. No significant association was observed for distal colon [ORQ4 vs Q1 (95% CI) 1.19 (0.98-1.45); P trend = 0.09]. Replacing one serving per day of preserved vegetables with fresh vegetables was related to 20%, 23%, and 37% lower prevalence of overall, small, and multiple polyps, respectively. CONCLUSIONS Preserved vegetable consumption was associated with a higher prevalence of colorectal polyps in a Chinese population at a high risk of CRC. Replacing preserved vegetables with fresh vegetables may be conducive to lower prevalent colorectal polyps.
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Affiliation(s)
- Fei Wu
- Department of Nutrition, School of Public Health, Department of Clinical Nutrition of Affiliated Second Hospital, Zhejiang University School of Medicine, HangzhouZhejiang, 310058, China
| | - Baoquan Wang
- Lanxi Red Cross Hospital, JinhuaZhejiang, 321000, China
| | - Pan Zhuang
- Zhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang University, HangzhouZhejiang, 310058, China
| | - Zhonghua Lu
- Lanxi Red Cross Hospital, JinhuaZhejiang, 321000, China
| | - Yin Li
- Department of Nutrition, School of Public Health, Department of Clinical Nutrition of Affiliated Second Hospital, Zhejiang University School of Medicine, HangzhouZhejiang, 310058, China
| | - Hongying Wang
- Lanxi Red Cross Hospital, JinhuaZhejiang, 321000, China
| | - Xiaohui Liu
- Department of Nutrition, School of Public Health, Department of Clinical Nutrition of Affiliated Second Hospital, Zhejiang University School of Medicine, HangzhouZhejiang, 310058, China
| | - Xuqiu Zhao
- Lanxi Red Cross Hospital, JinhuaZhejiang, 321000, China
| | - Wanshui Yang
- Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Jingjing Jiao
- Department of Nutrition, School of Public Health, Department of Clinical Nutrition of Affiliated Second Hospital, Zhejiang University School of Medicine, HangzhouZhejiang, 310058, China
| | - Weifang Zheng
- Lanxi Red Cross Hospital, JinhuaZhejiang, 321000, China.
| | - Yu Zhang
- Zhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang University, HangzhouZhejiang, 310058, China.
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9
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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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10
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Neumeyer S, Hua X, Seibold P, Jansen L, Benner A, Burwinkel B, Halama N, Berndt SI, Phipps AI, Sakoda LC, Schoen RE, Slattery ML, Chan AT, Gala M, Joshi AD, Ogino S, Song M, Herpel E, Bläker H, Kloor M, Scherer D, Ulrich A, Ulrich CM, Win AK, Figueiredo JC, Hopper JL, Macrae F, Milne RL, Giles GG, Buchanan DD, Peters U, Hoffmeister M, Brenner H, Newcomb PA, Chang-Claude J. Genetic Variants in the Regulatory T cell-Related Pathway and Colorectal Cancer Prognosis. Cancer Epidemiol Biomarkers Prev 2020; 29:2719-2728. [PMID: 33008876 PMCID: PMC7976673 DOI: 10.1158/1055-9965.epi-20-0714] [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: 05/11/2020] [Revised: 07/29/2020] [Accepted: 09/28/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND High numbers of lymphocytes in tumor tissue, including T regulatory cells (Treg), have been associated with better colorectal cancer survival. Tregs, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and therefore variants in genes related to Treg differentiation and function could be associated with colorectal cancer prognosis. METHODS In a prospective German cohort of 3,593 colorectal cancer patients, we assessed the association of 771 single-nucleotide polymorphisms (SNP) in 58 Treg-related genes with overall and colorectal cancer-specific survival using Cox regression models. Effect modification by microsatellite instability (MSI) status was also investigated because tumors with MSI show greater lymphocytic infiltration and have been associated with better prognosis. Replication of significant results was attempted in 2,047 colorectal cancer patients of the International Survival Analysis in Colorectal Cancer Consortium (ISACC). RESULTS A significant association of the TGFBR3 SNP rs7524066 with more favorable colorectal cancer-specific survival [hazard ratio (HR) per minor allele: 0.83; 95% confidence interval (CI), 0.74-0.94; P value: 0.0033] was replicated in ISACC (HR: 0.82; 95% CI, 0.68-0.98; P value: 0.03). Suggestive evidence for association was found with two IL7 SNPs, rs16906568 and rs7845577. Thirteen SNPs with differential associations with overall survival according to MSI in the discovery analysis were not confirmed. CONCLUSIONS Common genetic variation in the Treg pathway implicating genes such as TGFBR3 and IL7 was shown to be associated with prognosis of colorectal cancer patients. IMPACT The implicated genes warrant further investigation.
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Affiliation(s)
- Sonja Neumeyer
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Xinwei Hua
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
- School of Public Health, University of Washington, Seattle, Washington
| | - Petra Seibold
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Lina Jansen
- Division of Clinical Epidemiology and Aging Research, DKFZ, Heidelberg, Germany
| | - Axel Benner
- Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Barbara Burwinkel
- Division of Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Department of Gynecology and Obstetrics, Molecular Biology of Breast Cancer, University of Heidelberg, Heidelberg, Germany
| | - Niels Halama
- Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany
- Tissue Imaging and Analysis Center, National Center for Tumor Diseases, BIOQUANT, University of Heidelberg, Heidelberg, Germany
- Institute for Immunology, University Hospital Heidelberg, Heidelberg, Germany
| | - Sonja I Berndt
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
| | - Amanda I Phipps
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
- Epidemiology Department, University of Washington, Seattle, Washington
| | - Lori C Sakoda
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
- Division of Research, Kaiser Permanente Northern California, Oakland, California
| | - Robert E Schoen
- Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Martha L Slattery
- Department of Internal Medicine, University of Utah, Salt Lake City, Utah
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Manish Gala
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Amit D Joshi
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts
| | - Shuji Ogino
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
| | - Mingyang Song
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts
| | - Esther Herpel
- NCT Tissue Bank, National Center for Tumor Diseases (NCT), Heidelberg, Germany
- Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
| | - Hendrik Bläker
- Institute of Pathology, Charité University Medicine, Berlin, Germany
| | - Matthias Kloor
- Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
| | - Dominique Scherer
- Institute of Medical Biometry and Informatics, University Hospital Heidelberg, Heidelberg, Germany
| | - Alexis Ulrich
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University of Heidelberg, Germany
| | - Cornelia M Ulrich
- Huntsman Cancer Institute, Population Sciences, Salt Lake City, Utah
- Department of Population Health Sciences, University of Utah, Salt Lake City, Utah
| | - Aung K Win
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Melbourne, Australia
| | - Jane C Figueiredo
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles California
| | - John L Hopper
- Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Victoria, Australia
| | - Finlay Macrae
- Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Victoria, Australia
| | - Roger L Milne
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Melbourne, Australia
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
| | - Graham G Giles
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Melbourne, Australia
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
| | - Daniel D Buchanan
- Colorectal Oncogenomics Group, Department of Clinical Pathology, 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, Parkville, Victoria, Australia
| | - Ulrike Peters
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
- Department of Epidemiology, University of Washington, Seattle, Washington
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, DKFZ, Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, 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
| | - Polly A Newcomb
- Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Cancer Epidemiology Group, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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11
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Colonoscopy and Reduction of Colorectal Cancer Risk by Molecular Tumor Subtypes: A Population-Based Case-Control Study. Am J Gastroenterol 2020; 115:2007-2016. [PMID: 32858564 DOI: 10.14309/ajg.0000000000000819] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION In previous studies, the protective effect of colonoscopy was generally stronger for distal colorectal cancer than for proximal colorectal cancer (CRC). This study aimed to investigate whether reduction of CRC risk through colonoscopy varies according to major tumor markers and pathways of CRC. METHODS This is a population-based case-control study from Germany, including 2,132 patients with a first diagnosis of CRC and information on major molecular tumor markers and 2,486 control participants without CRC. Detailed participant characteristics were collected by standardized questionnaires. Information on previous colonoscopy was derived from medical records. Polytomous logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between previous colonoscopy and subtypes of CRC. RESULTS Overall, we observed strong risk reduction of CRC after colonoscopy that was weaker for microsatellite instable (MSI) than for non-MSI CRC (OR 0.70, 95% CI 0.50-0.97 vs OR 0.28, 95% CI 0.24-0.33), for CpG island methylator phenotype high CRC than for CpG island methylator phenotype low/negative CRC (OR 0.45, 95% CI 0.34-0.59 vs OR 0.29, 95% CI 0.25-0.34), for BRAF-mutated than for BRAF nonmutated CRC (OR 0.62, 95% CI 0.42-0.91 vs OR 0.30, 95% CI 0.25-0.35), for KRAS nonmutated than for KRAS-mutated CRC (OR 0.34, 95% CI 0.29-0.40 vs OR 0.26, 95% CI 0.20-0.32), and for CRC classified into the sessile serrated pathway than for CRC of the traditional pathway (OR 0.57, 95% CI 0.36-0.91 vs OR 0.30, 95% CI 0.25-0.37). After colonoscopy with the detection of adenomas or hyperplastic polyps, no risk reduction was found for sessile serrated pathway CRC, MSI, and BRAF-mutated subtypes. DISCUSSION Our study extends the molecular understanding of existing differences in risk reduction of proximal and distal CRCs reported by previous studies and may imply important information for improving strategies for timely detection of relevant precursors.
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12
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Gomes SD, Oliveira CS, Azevedo-Silva J, Casanova MR, Barreto J, Pereira H, Chaves SR, Rodrigues LR, Casal M, Côrte-Real M, Baltazar F, Preto A. The Role of Diet Related Short-Chain Fatty Acids in Colorectal Cancer Metabolism and Survival: Prevention and Therapeutic Implications. Curr Med Chem 2020; 27:4087-4108. [PMID: 29848266 DOI: 10.2174/0929867325666180530102050] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Revised: 12/22/2017] [Accepted: 05/15/2018] [Indexed: 12/16/2022]
Abstract
Colorectal Cancer (CRC) is a major cause of cancer-related death worldwide. CRC increased risk has been associated with alterations in the intestinal microbiota, with decreased production of Short Chain Fatty Acids (SCFAs). SCFAs produced in the human colon are the major products of bacterial fermentation of undigested dietary fiber and starch. While colonocytes use the three major SCFAs, namely acetate, propionate and butyrate, as energy sources, transformed CRC cells primarily undergo aerobic glycolysis. Compared to normal colonocytes, CRC cells exhibit increased sensitivity to SCFAs, thus indicating they play an important role in cell homeostasis. Manipulation of SCFA levels in the intestine, through changes in microbiota, has therefore emerged as a potential preventive/therapeutic strategy for CRC. Interest in understanding SCFAs mechanism of action in CRC cells has increased in the last years. Several SCFA transporters like SMCT-1, MCT-1 and aquaporins have been identified as the main transmembrane transporters in intestinal cells. Recently, it was shown that acetate promotes plasma membrane re-localization of MCT-1 and triggers changes in the glucose metabolism. SCFAs induce apoptotic cell death in CRC cells, and further mechanisms have been discovered, including the involvement of lysosomal membrane permeabilization, associated with mitochondria dysfunction and degradation. In this review, we will discuss the current knowledge on the transport of SCFAs by CRC cells and their effects on CRC metabolism and survival. The impact of increasing SCFA production by manipulation of colon microbiota on the prevention/therapy of CRC will also be addressed.
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Affiliation(s)
- Sara Daniela Gomes
- CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho,
Campus de Gualtar, 4710-057 Braga, Portugal,ICVS - Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal
| | - Cláudia Suellen Oliveira
- CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho,
Campus de Gualtar, 4710-057 Braga, Portugal,ICBAS - Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal
| | - João Azevedo-Silva
- CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho,
Campus de Gualtar, 4710-057 Braga, Portugal
| | - Marta R Casanova
- CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho,
Campus de Gualtar, 4710-057 Braga, Portugal,CEB - Centre of Biological Engineering, University of Minho, Braga, Portugal
| | - Judite Barreto
- CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho,
Campus de Gualtar, 4710-057 Braga, Portugal
| | - Helena Pereira
- CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho,
Campus de Gualtar, 4710-057 Braga, Portugal
| | - Susana R Chaves
- CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho,
Campus de Gualtar, 4710-057 Braga, Portugal
| | - Lígia R Rodrigues
- CEB - Centre of Biological Engineering, University of Minho, Braga, Portugal
| | - Margarida Casal
- CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho,
Campus de Gualtar, 4710-057 Braga, Portugal
| | - Manuela Côrte-Real
- CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho,
Campus de Gualtar, 4710-057 Braga, Portugal
| | - Fátima Baltazar
- ICVS - Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal,ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Ana Preto
- CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho,
Campus de Gualtar, 4710-057 Braga, Portugal
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13
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Labadie JD, Harrison TA, Banbury B, Amtay EL, Bernd S, Brenner H, Buchanan DD, Campbell PT, Cao Y, Chan AT, Chang-Claude J, English D, Figueiredo JC, Gallinger SJ, Giles GG, Gunter MJ, Hoffmeister M, Hsu L, Jenkins MA, Lin Y, Milne RL, Moreno V, Murphy N, Ogino S, Phipps AI, Sakoda LC, Slattery ML, Southey MC, Sun W, Thibodeau SN, Van Guelpen B, Zaidi SH, Peters U, Newcomb PA. Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location. JNCI Cancer Spectr 2020; 4:pkaa042. [PMID: 32923935 PMCID: PMC7477374 DOI: 10.1093/jncics/pkaa042] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 04/20/2020] [Accepted: 05/12/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. METHODS We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2-sided. RESULTS Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; P het =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; P het =.01) tumors. CONCLUSIONS We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors.
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Affiliation(s)
- Julia D Labadie
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Tabitha A Harrison
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Barbara Banbury
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Efrat L Amtay
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Sonja Bernd
- 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
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Daniel D Buchanan
- Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia
| | - Peter T Campbell
- Behavioral and Epidemiology Research Group, 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, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany
| | - Dallas English
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Jane C Figueiredo
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai, Los Angeles, CA, USA
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Steven J Gallinger
- Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Graham G Giles
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Marc J Gunter
- Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Li Hsu
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Biostatistics, University of Washington, Seattle, WA, USA
| | - Mark A Jenkins
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Yi Lin
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Roger L Milne
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Victor Moreno
- Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain
| | - Neil Murphy
- Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, 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
| | - Martha L Slattery
- Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA
| | - Melissa C Southey
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
- Genetic Epidemiology Laboratory, Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria, Australia
| | - Wei Sun
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Stephen N Thibodeau
- Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Bethany Van Guelpen
- Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
| | - Syed H Zaidi
- Ontario Institute for Cancer Research, Toronto, Ontario, Canada
| | - Ulrike Peters
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, 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
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14
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El Asri A, Zarrouq B, El Kinany K, Bouguenouch L, Ouldim K, El Rhazi K. Associations between nutritional factors and KRAS mutations in colorectal cancer: a systematic review. BMC Cancer 2020; 20:696. [PMID: 32723394 PMCID: PMC7388532 DOI: 10.1186/s12885-020-07189-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 07/16/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Between 30 and 50% of colon tumors have mutations in the Kirsten-ras (KRAS) gene, which have a large nutritional attributable risk. Despite its high frequency in colorectal cancer (CRC), data to support specific associations between KRAS mutations in CRC and diet are sparse. Here, we conducted a systematic review to summarize the current epidemiological evidence on the association between various dietary factors and KRAS mutations. METHODS PubMed, Science Direct, and Cochrane databases were searched for relevant studies published until December 31, 2019, using inclusion and exclusion criteria in accordance with PRISMA guidelines. We analyzed the studies to find associations between nutritional factors and CRC tumors with KRAS mutations in humans. RESULTS We identified 28 relevant studies to include in this systematic review. In-depth analyses showed unclear associations between nutritional factors and KRAS mutations in CRC. Most epidemiological studies in the same nutrient or food often reported conflicting and/or inconclusive findings, whereas for some dietary factors, the results were homogeneous. CONCLUSIONS Further research using a more robust prospective cohort study is needed to lend more credence to the epidemiological associations found between KRAS mutations and dietary factors.
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Affiliation(s)
- Achraf El Asri
- Laboratory of Epidemiology and Research in Health Sciences, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdallah University, Fez, Morocco
- Medical Genetics and Oncogenetics Unit, Hassan II University Hospital, Fez, Morocco
| | - Btissame Zarrouq
- Laboratory of Epidemiology and Research in Health Sciences, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdallah University, Fez, Morocco
- Teacher’s Training College (Ecole Normale Superieure), Department of Biology and Geology, Sidi Mohammed Ben Abdallah University, Fez, Morocco
| | - Khaoula El Kinany
- Laboratory of Epidemiology and Research in Health Sciences, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdallah University, Fez, Morocco
| | - Laila Bouguenouch
- Medical Genetics and Oncogenetics Unit, Hassan II University Hospital, Fez, Morocco
| | - Karim Ouldim
- Medical Genetics and Oncogenetics Unit, Hassan II University Hospital, Fez, Morocco
- Cancer Research Institute, Fez, Morocco
| | - Karima El Rhazi
- Laboratory of Epidemiology and Research in Health Sciences, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdallah University, Fez, Morocco
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15
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Carr PR, Weigl K, Edelmann D, Jansen L, Chang-Claude J, Brenner H, Hoffmeister M. Estimation of Absolute Risk of Colorectal Cancer Based on Healthy Lifestyle, Genetic Risk, and Colonoscopy Status in a Population-Based Study. Gastroenterology 2020; 159:129-138.e9. [PMID: 32179093 PMCID: PMC7387145 DOI: 10.1053/j.gastro.2020.03.016] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 03/04/2020] [Accepted: 03/07/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND & AIMS Estimates of absolute risk of colorectal cancer (CRC) are needed to facilitate communication and better inform the public about the potentials and limits of cancer prevention. METHODS Using data from a large population-based case-control study in Germany (Darmkrebs: Chancen der Verhütung durch Screening [DACHS] study, which began in 2003) and population registry data, we calculated 30-year absolute risk estimates for development of CRC based on a healthy lifestyle score (derived from 5 modifiable lifestyle factors: smoking, alcohol consumption, diet, physical activity, and body fatness), a polygenic risk score (based on 90 single-nucleotide polymorphisms), and colonoscopy history. RESULTS We analyzed data from 4220 patients with CRC and 3338 individuals without CRC. Adherence to a healthy lifestyle and colonoscopy in the preceding 10 years were associated with a reduced relative risk of CRC in men and women. We observed a higher CRC risk in participants with high or intermediate genetic risk scores. For 50-year-old men and women without a colonoscopy, the absolute risk of CRC varied according to the polygenic risk score and the healthy lifestyle score (men, 3.5%-13.4%; women, 2.5%-10.6%). For 50-year-old men and women with a colonoscopy, the absolute risk of developing CRC was much lower but still varied according to the polygenic risk score and the healthy lifestyle score (men, 1.2%-4.8%; women, 0.9%-4.2%). Among all risk factor profiles, the 30-year absolute risk estimates consistently decreased with adherence to a healthy lifestyle. CONCLUSIONS In a population-based study, we found that a colonoscopy can drastically reduce the absolute risk of CRC and that the genetically predetermined risk of CRC can be further reduced by adherence to a healthy lifestyle. Our results show the magnitude of CRC prevention possible through colonoscopy and lifestyle at a predefined genetic risk. This observational study has been registered in the German Clinical Trials Register (DRKS00011793), which is a primary registry in the World Health Organization Registry Network.
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Affiliation(s)
- Prudence R Carr
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
| | - Korbinian Weigl
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany, 69120,German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany, 69120
| | - Dominic Edelmann
- Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany, 69120
| | - Lina Jansen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany, 69120
| | - Jenny Chang-Claude
- Genetic Tumour Epidemiology Group, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Hamburg, Germany, 20246,Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany, 69120
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany, 69120,German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany, 69120,Division of Preventive Oncology, German Cancer Research Center, Heidelberg, Germany, 69120
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany, 69120
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16
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Phipps AI, Alwers E, Harrison T, Banbury B, Brenner H, Campbell PT, Chang-Claude J, Buchanan D, Chan AT, Farris AB, Figueiredo JC, Gallinger S, Giles GG, Jenkins M, Milne RL, Newcomb PA, Slattery ML, Song M, Ogino S, Zaidi SH, Hoffmeister M, Peters U. Association Between Molecular Subtypes of Colorectal Tumors and Patient Survival, Based on Pooled Analysis of 7 International Studies. Gastroenterology 2020; 158:2158-2168.e4. [PMID: 32088204 PMCID: PMC7282955 DOI: 10.1053/j.gastro.2020.02.029] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 01/31/2020] [Accepted: 02/12/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS The heterogeneity among colorectal tumors is probably due to differences in developmental pathways and might associate with patient survival times. We studied the relationship among markers of different subtypes of colorectal tumors and patient survival. METHODS We pooled data from 7 observational studies, comprising 5010 patients with colorectal cancer. All the studies collected information on microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and mutations in KRAS and BRAF in tumors. Tumors with complete marker data were classified as type 1 (MSI-high, CIMP-positive, with pathogenic mutations in BRAF but not KRAS), type 2 (not MSI-high, CIMP-positive, with pathogenic mutations in BRAF but not KRAS), type 3 (not MSI-high or CIMP, with pathogenic mutations in KRAS but not BRAF), type 4 (not MSI-high or CIMP, no pathogenic mutations in BRAF or KRAS), or type 5 (MSI-high, no CIMP, no pathogenic mutations in BRAF or KRAS). We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for associations of these subtypes and tumor markers with disease-specific survival (DSS) and overall survival times, adjusting for age, sex, stage at diagnosis, and study population. RESULTS Patients with type 2 colorectal tumors had significantly shorter time of DSS than patients with type 4 tumors (HRDSS 1.66; 95% CI 1.33-2.07), regardless of sex, age, or stage at diagnosis. Patients without MSI-high tumors had significantly shorter time of DSS compared with patients with MSI-high tumors (HRDSS 0.42; 95% CI 0.27-0.64), regardless of other tumor markers or stage, or patient sex or age. CONCLUSIONS In a pooled analysis of data from 7 observational studies of patients with colorectal cancer, we found that tumor subtypes, defined by combinations of 4 common tumor markers, were associated with differences in survival time. Colorectal tumor subtypes might therefore be used in determining patients' prognoses.
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Affiliation(s)
- Amanda I. Phipps
- Epidemiology Department, University of Washington, Seattle, WA,Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Elizabeth Alwers
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Tabitha Harrison
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Barbara Banbury
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany,Division 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
| | - Peter T. Campbell
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany,Cancer Epidemiology Group, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Hamburg, Germany
| | - Daniel Buchanan
- Department of Clinical Pathology, Colorectal Oncogenomics Group, The University of Melbourne, Parkville, Victoria, Australia
| | - Andrew T. Chan
- Clinical and Translational Epidemiology Unit, Department of Medicine, and Division of Gastroenterology, Massachusetts General Hospital, Boston, MA,Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | | | - Jane C. Figueiredo
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Steven Gallinger
- Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Graham G. Giles
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia,Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia,Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Mark Jenkins
- Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Roger L. Milne
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia,Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia,Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Polly A. Newcomb
- Epidemiology Department, University of Washington, Seattle, WA,Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | | | - Mingyang Song
- Clinical and Translational Epidemiology Unit, Department of Medicine, and Division of Gastroenterology, Massachusetts General Hospital, Boston, MA,Departments of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Shuji Ogino
- Departments of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA,Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA,Broad Institute of MIT and Harvard, Cambridge, MA
| | - Syed H. Zaidi
- Ontario Institute for Cancer Research, Toronto, Ontario, Canada
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Ulrike Peters
- Epidemiology Department, University of Washington, Seattle, WA,Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
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Hoffmeister M. New insights into the association of meat intake and sessile serrated lesions of the large bowel. Am J Clin Nutr 2020; 111:1117-1118. [PMID: 32297917 DOI: 10.1093/ajcn/nqaa077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Michael Hoffmeister
- Molecular Pathological Epidemiology, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
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18
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Wang ST, Cui WQ, Pan D, Jiang M, Chang B, Sang LX. Tea polyphenols and their chemopreventive and therapeutic effects on colorectal cancer. World J Gastroenterol 2020; 26:562-597. [PMID: 32103869 PMCID: PMC7029350 DOI: 10.3748/wjg.v26.i6.562] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 12/30/2019] [Accepted: 01/11/2020] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC), a multifactorial disease, is usually induced and developed through complex mechanisms, including impact of diet and lifestyle, genomic abnormalities, change of signaling pathways, inflammatory response, oxidation stress, dysbiosis, and so on. As natural polyphenolic phytochemicals that exist primarily in tea, tea polyphenols (TPs) have been shown to have many clinical applications, especially as anticancer agents. Most animal studies and epidemiological studies have demonstrated that TPs can prevent and treat CRC. TPs can inhibit the growth and metastasis of CRC by exerting the anti-inflammatory, anti-oxidative or pro-oxidative, and pro-apoptotic effects, which are achieved by modulations at multiple levels. Many experiments have demonstrated that TPs can modulate several signaling pathways in cancer cells, including the mitogen-activated protein kinase pathway, phosphatidylinositol-3 kinase/Akt pathway, Wnt/β-catenin pathway, and 67 kDa laminin receptor pathway, to inhibit proliferation and promote cell apoptosis. In addition, novel studies have also suggested that TPs can prevent the growth and metastasis of CRC by modulating the composition of gut microbiota to improve immune system and decrease inflammatory responses. Molecular pathological epidemiology, a novel multidisciplinary investigation, has made great progress on CRC, and the further molecular pathological epidemiology research should be developed in the field of TPs and CRC. This review summarizes the existing in vitro and in vivo animal and human studies and potential mechanisms to examine the effects of tea polyphenols on CRC.
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Affiliation(s)
- Shi-Tong Wang
- Department of Cardiovascular Ultrasound, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Wen-Qi Cui
- Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Dan Pan
- Department of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Min Jiang
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Bing Chang
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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19
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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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20
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Mortality trends of colorectal cancer among overweight patients at the global and national levels. Int J Colorectal Dis 2019; 34:1689-1695. [PMID: 31468109 DOI: 10.1007/s00384-019-03371-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/23/2019] [Indexed: 02/04/2023]
Abstract
PURPOSE Colorectal cancer (CRC) is a commonly diagnosed malignancy with highly heterogeneous incidence and mortality rates worldwide. High body mass index (BMI) is a well-defined risk factor for CRC. The mortality trends of CRC among patients who are overweight contributions at the global and national levels are largely unknown. METHOD We collected data on CRC-related mortality attributable to high BMI from 1990 to 2017 from the Global Burden of Disease Study 2017 database. The annual average percentage change (AAPC) was used to quantify the CRC age-standardized mortality rate (ASMR) trends. RESULTS Globally, approximately 896,040 CRC-related deaths occurred in 2017, among which 73,222 (8.2%; 54,193 in men and 19,029 in women) deaths were attributable to high BMI. The high-BMI-related CRC ASMR increased from 0.81 per 100,000 in 1990 to 0.93 per 100,000 in 2017, with an AAPC of 0.42 (95% CI 0.36, 0.49). The increasing trend was consistent among populations of different sexes and ages. A more pronounced increase was found in men and in regions with middle or low socio-demographic indexes. CONCLUSION The increase in high-BMI-related CRC mortality suggests scarce attention to overweight in the current prevention strategies and highlights its priority in future prevention strategies for CRC.
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21
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Association Between Intake of Red and Processed Meat and Survival in Patients With Colorectal Cancer in a Pooled Analysis. Clin Gastroenterol Hepatol 2019; 17:1561-1570.e3. [PMID: 30476588 PMCID: PMC6533164 DOI: 10.1016/j.cgh.2018.11.036] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 11/14/2018] [Accepted: 11/16/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Red and processed meat intake is associated with colorectal cancer (CRC) incidence, but it is not clear if intake is associated with patient survival after diagnosis. METHODS We pooled data from 7627 patients with stage I-IV CRC from 10 studies in the International Survival Analysis in Colorectal Cancer Consortium. Cox proportional hazards regression models were used to evaluate the associations of intake of red and processed meat before diagnosis with overall and CRC-specific survival. RESULTS Among 7627 patients with CRC, 2338 died, including 1576 from CRC, over a median follow-up time of 5.1 years. In multivariable-adjusted analyses, higher intake of red or processed meat was not associated with overall survival of patients with stage I-III CRC: Q4 vs Q1 red meat hazard ratio [HR], 1.08 (95% CI, 0.93-1.26) and Q4 vs Q1 processed meat HR, 1.10 (95% CI, 0.93-1.32) or with CRC-specific survival: Q4 vs Q1 red meat HR, 1.09 (95% CI, 0.89-1.33) and Q4 vs Q1 processed meat HR, 1.11 (95% CI, 0.87-1.42). Results were similar for patients with stage IV CRC. However, patients with stage I-III CRC who reported an intake of processed meat above the study-specific medians had a higher risk of death from any cause (HR, 1.12; 95% CI, 1.01-1.25) than patients who reported eating at or less than the median. CONCLUSION In this large consortium of CRC patient cohorts, intake of red and processed meat before a diagnosis of CRC was not associated with shorter survival time after diagnosis, although a possible weak adverse association cannot be excluded. Studies that evaluate dietary data from several time points before and after cancer diagnosis are required to confirm these findings.
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Neumeyer S, Popanda O, Edelmann D, Butterbach K, Toth C, Roth W, Bläker H, Jiang R, Herpel E, Jäkel C, Schmezer P, Jansen L, Alwers E, Benner A, Burwinkel B, Hoffmeister M, Brenner H, Chang-Claude J. Genome-wide DNA methylation differences according to oestrogen receptor beta status in colorectal cancer. Epigenetics 2019; 14:477-493. [PMID: 30931802 DOI: 10.1080/15592294.2019.1595998] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Involvement of sex hormones in colorectal cancer (CRC) development has been linked to oestrogen receptor β (ERβ). Expression of ERβ is found reduced in tumour tissue and inversely related to mortality. However, mechanisms are not well understood. Our study aimed to detect differentially methylated genes associated with ERβ expression, which could point to mechanisms by which ERβ could influence risk and prognosis of CRC. Epigenome-wide DNA methylation profiling was performed using Illumina HumanMethylation450k BeadChip arrays in two independent tumour sample sets of CRC patients recruited in 2003-2010 by the German DACHS study (discovery cohort n = 917, replication cohort n = 907). ERβ expression was measured using immunohistochemistry and scored as negative, moderate and high. Differentially methylated CpG sites and genomic regions were determined using limma in the R-package RnBeads. For the comparison of tumours with moderate/high ERβ versus negative expression, differentially methylated CpG sites were identified but not confirmed by replication. Comparing tumours of high with tumours of negative ERβ expression revealed 2,904 differentially methylated CpG sites of which 403 were replicated (FDR adjusted p-value<0.05). Replicated CpGs were annotated to genes such as CD36, HK1 or LRP5. A survival analysis indicates that 30 of the replicated CpGs are also associated with overall survival (FDR-adjusted p-value<0.05). The regional analysis identified 60 differentially methylated promotor regions. The epigenome-wide analysis identified both novel genes as well as genes already implicated in CRC. Follow-up mechanistic studies to better understand the regulatory role of ERβ could inform potential targets for improving treatment or prevention of CRC.
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Affiliation(s)
- Sonja Neumeyer
- a Division of Cancer Epidemiology , German Cancer Research Center , Heidelberg , Germany.,b Medical Faculty Heidelberg , Heidelberg University , Heidelberg , Germany
| | - Odilia Popanda
- c Division of Epigenomics and Cancer Risk Factors , German Cancer Research Center , Heidelberg , Germany
| | - Dominic Edelmann
- d Division of Biostatistics , German Cancer Research Center , Heidelberg , Germany
| | - Katja Butterbach
- a Division of Cancer Epidemiology , German Cancer Research Center , Heidelberg , Germany.,e Division of Clinical Epidemiology and Aging Research , German Cancer Research Center , Heidelberg , Germany
| | - Csaba Toth
- f Institute of Pathology , Heidelberg University , Heidelberg , Germany
| | - Wilfried Roth
- g Institute of Pathology , Universitätsmedizin der Johannes Gutenberg-Universität Mainz , Mainz , Germany
| | - Hendrik Bläker
- h Institute of Pathology , Charité University Medicine , Berlin , Germany
| | - Ruijingfang Jiang
- a Division of Cancer Epidemiology , German Cancer Research Center , Heidelberg , Germany
| | - Esther Herpel
- f Institute of Pathology , Heidelberg University , Heidelberg , Germany.,i NCT Tissue Bank , National Center for Tumor Diseases (NCT) , Heidelberg , Germany
| | - Cornelia Jäkel
- c Division of Epigenomics and Cancer Risk Factors , German Cancer Research Center , Heidelberg , Germany
| | - Peter Schmezer
- c Division of Epigenomics and Cancer Risk Factors , German Cancer Research Center , Heidelberg , Germany
| | - Lina Jansen
- e Division of Clinical Epidemiology and Aging Research , German Cancer Research Center , Heidelberg , Germany
| | - Elizabeth Alwers
- e Division of Clinical Epidemiology and Aging Research , German Cancer Research Center , Heidelberg , Germany
| | - Axel Benner
- d Division of Biostatistics , German Cancer Research Center , Heidelberg , Germany
| | - Barbara Burwinkel
- j Division of Molecular Epidemiology , German Cancer Research Center (DKFZ) , Heidelberg , Germany.,k Department of Gynecology and Obstetrics, Molecular Biology of Breast Cancer , University of Heidelberg , Heidelberg , Germany
| | - Michael Hoffmeister
- e Division of Clinical Epidemiology and Aging Research , German Cancer Research Center , Heidelberg , Germany
| | - Hermann Brenner
- e Division of Clinical Epidemiology and Aging Research , German Cancer Research Center , Heidelberg , Germany.,l Division of Preventive Oncology , German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT) , Heidelberg , Germany.,m German Cancer Consortium (DKTK) , German Cancer Research Center (DKFZ) , Heidelberg , Germany
| | - Jenny Chang-Claude
- a Division of Cancer Epidemiology , German Cancer Research Center , Heidelberg , Germany.,n Cancer Epidemiology Group , University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf , Hamburg , Germany
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Carr PR, Weigl K, Jansen L, Walter V, Erben V, Chang-Claude J, Brenner H, Hoffmeister M. Healthy Lifestyle Factors Associated With Lower Risk of Colorectal Cancer Irrespective of Genetic Risk. Gastroenterology 2018; 155:1805-1815.e5. [PMID: 30201362 PMCID: PMC6279591 DOI: 10.1053/j.gastro.2018.08.044] [Citation(s) in RCA: 98] [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: 03/20/2018] [Revised: 08/17/2018] [Accepted: 08/26/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS The combined effects of healthy lifestyle factors on colorectal cancer (CRC) risk are unclear. We aimed to develop a healthy lifestyle score, to investigate the joint effects of modifiable lifestyle factors on reduction of CRC risk and determine whether associations differ with genetic risk. METHODS We collected data from a large population-based case-control study in Germany and used multiple logistic regression analyses to examine associations between the healthy lifestyle score (derived from 5 modifiable lifestyle factors: smoking, alcohol consumption, diet, physical activity, and body fatness) and CRC risk. We created a genetic risk score, based on 53 risk variants, to investigate the association of the healthy lifestyle score and risk of CRC, stratified by genetic risk. RESULTS We included 4092 patients with CRC and 3032 individuals without CRC (controls) in our analysis. In adjusted models, compared with participants with 0 or 1 healthy lifestyle factor, participants with 2 (odds ratio [OR] 0.85; 95% confidence interval [CI] 0.67-1.06), 3 (OR 0.62; 95% CI 0.50-0.77), 4 (OR 0.53; 95% CI 0.42-0.66), or 5 (OR 0.33; 95% CI 0.26-0.43) healthy lifestyle factors had increasingly lower risks of CRC (P trend <.0001). We found no differences among subgroups stratified by genetic risk score, history of colonoscopy, or family history of CRC. Overall, 45% of CRC cases (95% CI 34%-53%) could be attributed to nonadherence to all 5 healthy lifestyle behaviors. CONCLUSIONS In a large population-based case-control study, we identified a combination of lifestyle factors that appears to reduce risk of CRC, regardless of the patient's genetic profile. These results reinforce the importance of primary prevention of CRC.
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Affiliation(s)
- Prudence R Carr
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
| | - Korbinian Weigl
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany; Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Lina Jansen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Viola Walter
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Vanessa Erben
- Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center, Heidelberg, Germany
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; Genetic Tumour Epidemiology Group, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Hamburg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center, Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
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Pandurangan AK, Divya T, Kumar K, Dineshbabu V, Velavan B, Sudhandiran G. Colorectal carcinogenesis: Insights into the cell death and signal transduction pathways: A review. World J Gastrointest Oncol 2018; 10:244-259. [PMID: 30254720 PMCID: PMC6147765 DOI: 10.4251/wjgo.v10.i9.244] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Revised: 06/05/2018] [Accepted: 06/28/2018] [Indexed: 02/05/2023] Open
Abstract
Colorectal carcinogenesis (CRC) imposes a major health burden in developing countries. It is the third major cause of cancer deaths. Despite several treatment strategies, novel drugs are warranted to reduce the severity of this disease. Adenomatous polyps in the colon are the major culprits in CRC and found in 45% of cancers, especially in patients 60 years of age. Inflammatory polyps are currently gaining attention in CRC, and a growing body of evidence denotes the role of inflammation in CRC. Several experimental models are being employed to investigate CRC in animals, which include the APCmin/+ mouse model, Azoxymethane, Dimethyl hydrazine, and a combination of Dextran sodium sulphate and dimethyl hydrazine. During CRC progression, several signal transduction pathways are activated. Among the major signal transduction pathways are p53, Transforming growth factor beta, Wnt/β-catenin, Delta Notch, Hippo signalling, nuclear factor erythroid 2-related factor 2 and Kelch-like ECH-associated protein 1 pathways. These signalling pathways collaborate with cell death mechanisms, which include apoptosis, necroptosis and autophagy, to determine cell fate. Extensive research has been carried out in our laboratory to investigate these signal transduction and cell death mechanistic pathways in CRC. This review summarizes CRC pathogenesis and the related cell death and signal transduction pathways.
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Affiliation(s)
- Ashok kumar Pandurangan
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
- School of Life sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai 600048, India
| | - Thomas Divya
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
| | - Kalaivani Kumar
- School of Life sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai 600048, India
| | - Vadivel Dineshbabu
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
| | - Bakthavatchalam Velavan
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
| | - Ganapasam Sudhandiran
- Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
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Benarba B. Red and processed meat and risk of colorectal cancer: an update. EXCLI JOURNAL 2018; 17:792-797. [PMID: 30190669 PMCID: PMC6123610 DOI: 10.17179/excli2018-1554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2018] [Accepted: 08/06/2018] [Indexed: 11/21/2022]
Affiliation(s)
- Bachir Benarba
- Laboratory Research on Biological Systems and Geomatics, Faculty of Nature and Life,University of Mascara, Algeria
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Garcia-Larsen V, Morton V, Norat T, Moreira A, Potts JF, Reeves T, Bakolis I. Dietary patterns derived from principal component analysis (PCA) and risk of colorectal cancer: a systematic review and meta-analysis. Eur J Clin Nutr 2018; 73:366-386. [DOI: 10.1038/s41430-018-0234-7] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Revised: 05/16/2018] [Accepted: 05/25/2018] [Indexed: 12/12/2022]
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Gianfredi V, Salvatori T, Villarini M, Moretti M, Nucci D, Realdon S. Is dietary fibre truly protective against colon cancer? A systematic review and meta-analysis. Int J Food Sci Nutr 2018. [PMID: 29516760 DOI: 10.1080/09637486.2018.1446917] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Colorectal cancer is the third most common cancer worldwide. Growing evidence shows that about 47% of cases of colorectal cancer can be prevented by a healthy lifestyle. We performed a systematic review and meta-analysis aimed to evaluate the association between dietary fibre intake and the risk of colon cancer. We performed a structured computer search on PubMed, including epidemiological studies reporting results of dietary fibre intake and risk of colon cancer in women or men. We compared subjects exposed to the highest versus the lowest consumption. The search strategy identified 376 papers. After screening, 25 datasets were included in our meta-analysis. Results suggest a protective role of dietary fibre intake on colon cancer risk ES = 0.74 (95% CI = 0.67-0.82), p value = .000, but, moderate statistical heterogeneity (χ2 = 42.73, p value = .011) was found. Due to the high mortality of colorectal cancer, it is important to identify effective preventive measures, especially those of a healthy lifestyle, such as a healthy diet.
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Affiliation(s)
- Vincenza Gianfredi
- a Graduate School of Hygiene and Preventive Medicine, Department of Experimental Medicine , University of Perugia , Perugia , Italy
| | - Tania Salvatori
- b Department of Pharmaceutical Science , University of Perugia , Perugia , Italy
| | - Milena Villarini
- b Department of Pharmaceutical Science , University of Perugia , Perugia , Italy
| | - Massimo Moretti
- b Department of Pharmaceutical Science , University of Perugia , Perugia , Italy
| | - Daniele Nucci
- c Digestive Endoscopy Unit, Veneto Institute of Oncology IOV-IRCCS , Padua , Italy
| | - Stefano Realdon
- c Digestive Endoscopy Unit, Veneto Institute of Oncology IOV-IRCCS , Padua , Italy
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Review: Dairy foods, red meat and processed meat in the diet: implications for health at key life stages. Animal 2018; 12:1709-1721. [DOI: 10.1017/s1751731118000642] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Koriem KMM. Protective effect of natural products and hormones in colon cancer using metabolome: A physiological overview. Asian Pac J Trop Biomed 2017. [DOI: 10.1016/j.apjtb.2017.09.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
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