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Munigala S, Bowe B, Subramaniam DS, Xian H, Gowda AN, Sheth SG, Chhabra R, Burroughs TE, Agarwal B. Assessing NODM Patients for Early PDAC Diagnosis: Incidence of NODM Before PDAC Diagnosis and Subsequent PDAC Risk. Cancer Med 2025; 14:e70878. [PMID: 40351037 PMCID: PMC12066942 DOI: 10.1002/cam4.70878] [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: 11/14/2024] [Revised: 02/11/2025] [Accepted: 04/04/2025] [Indexed: 05/14/2025] Open
Abstract
BACKGROUND New-Onset Diabetes Mellitus (NODM) is often an early manifestation of pancreatic cancer (Pancreatic Ductal Adenocarcinoma, PDAC). However, there is limited information about (1) the duration prior to PDAC diagnosis when the annual incidence of NODM starts significantly exceeding that in age-matched controls, (2) the percentage of PDAC patients diagnosed with NODM in the years preceding, and (3) the risk of PDAC following NODM in time when the PDAC risk is significantly higher than in controls. METHODS Using the nationwide VA database, we evaluated the annual incidence of NODM for 15 years preceding the PDAC diagnosis and in the age- and sex-matched controls (1:5 matching). In the second part, we evaluated the long-term risk and predictors of PDAC in NODM patients and controls. RESULTS The case-control study comprised 8198 PDAC patients and 40,992 matched controls. The higher annual incidence of NODM in PDAC patients was statistically significant up to 15 years before PDAC diagnosis. 69.2% of PDAC patients had NODM in the preceding 15 years versus 38.0% of controls. PDAC risk in the 15 years following NODM was 0.60% compared to 0.13% in the controls (aHR 3.83, 95% CI 3.68-3.98, p < 0.001). The risk of PDAC is more pronounced in the 1 year following NODM (aHR 9.07, 95% CI 8.33-9.87) than the subsequent 5 years (aHR 2.98, 95% CI 2.82-3.15). CONCLUSION NODM pre-dates PDAC diagnosis in most patients with PDAC. Further evaluation of NODM patients for PDAC has the potential to become a feasible strategy for diagnosing more early-stage resectable PDACs.
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Affiliation(s)
- Satish Munigala
- College for Public Health and Social JusticeSaint Louis UniversitySaint LouisMissouriUSA
- Department of Internal MedicineWashington University in St. LouisSaint LouisMissouriUSA
| | - Benjamin Bowe
- Clinical Epidemiology Center, Research and Education Service, VA Saint Louis, Health Care SystemSaint LouisMissouriUSA
| | - Divya S. Subramaniam
- Department of Health and Clinical Outcomes ResearchSaint Louis University School of MedicineSaint LouisMissouriUSA
- Advanced HEAlth Data (AHEAD) InstituteSaint Louis UniversitySaint LouisMissouriUSA
| | - Hong Xian
- Department of Epidemiology & Biostatistics, College for Public Health and Social JusticeSaint Louis UniversitySaint LouisMissouriUSA
| | | | - Sunil G. Sheth
- Beth Israel Deaconess Medical Center, and Harvard Medical SchoolBostonMassachusettsUSA
| | - Rajiv Chhabra
- Saint Luke's Hospital and University of Missouri Kansas CityKansas CityMissouriUSA
| | - Thomas E. Burroughs
- College for Public Health and Social JusticeSaint Louis UniversitySaint LouisMissouriUSA
- Department of Internal MedicineWashington University in St. LouisSaint LouisMissouriUSA
| | - Banke Agarwal
- Department of GastroenterologySSM St. Anthony's HospitalOklahoma CityOklahomaUSA
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Wu J, Tang L, Zheng F, Chen X, Li L. A review of the last decade: pancreatic cancer and type 2 diabetes. Arch Physiol Biochem 2024; 130:660-668. [PMID: 37646618 DOI: 10.1080/13813455.2023.2252204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 08/04/2023] [Accepted: 08/21/2023] [Indexed: 09/01/2023]
Abstract
Pancreatic cancer (PC) is a prevalent gastrointestinal tumour known for its high degree of malignancy, resulting in a mere 10% five-year survival rate for most patients. Over the past decade, a growing body of research has shed light on the intricate bidirectional association between PC and Type 2 diabetes (T2DM). The collection of PC- and T2DM-related articles is derived from two comprehensive databases, namely WOS (Web of Science Core Collection) and CNKI (China National Knowledge Infrastructure). This article discusses the last 10 years of research trends in PC and T2DM and explores their potential regulatory relationship as well as related medications.
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Affiliation(s)
- Jiaqi Wu
- Nanfang Hospital, Southern Medical University, Guangzhou, China
- School of Nursing, Southern Medical University, Guangzhou, China
| | - Liang Tang
- Department of General Medicine, Zhuzhou Central Hospital, Zhuzhou, China
| | - Feng Zheng
- Department of Anatomy, University of Otago, Dunedin, New Zealand
| | - Xun Chen
- Department of the Trauma center, Zhuzhou Central Hospital, Zhuzhou, China
- Department of hepatobiliary surgery, Zhuzhou Central Hospital, Zhuzhou, China
| | - Lei Li
- Department of Pathology, University of Otago, Dunedin, New Zealand
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Tan MCB, Isom CA, Liu Y, Trégouët DA, Wu L, Zhou D, Gamazon ER. Transcriptome-wide association study and Mendelian randomization in pancreatic cancer identifies susceptibility genes and causal relationships with type 2 diabetes and venous thromboembolism. EBioMedicine 2024; 106:105233. [PMID: 39002386 PMCID: PMC11284564 DOI: 10.1016/j.ebiom.2024.105233] [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: 01/18/2024] [Revised: 06/19/2024] [Accepted: 06/25/2024] [Indexed: 07/15/2024] Open
Abstract
BACKGROUND Two important questions regarding the genetics of pancreatic adenocarcinoma (PDAC) are 1. Which germline genetic variants influence the incidence of this cancer; and 2. Whether PDAC causally predisposes to associated non-malignant phenotypes, such as type 2 diabetes (T2D) and venous thromboembolism (VTE). METHODS In this study of 8803 patients with PDAC and 67,523 controls, we first performed a large-scale transcriptome-wide association study to investigate the association between genetically determined gene expression in normal pancreas tissue and PDAC risk. Secondly, we used Mendelian Randomization (MR) to analyse the causal relationships among PDAC, T2D (74,124 cases and 824,006 controls) and VTE (30,234 cases and 172,122 controls). FINDINGS Sixteen genes showed an association with PDAC risk (FDR <0.10), including six genes not yet reported for PDAC risk (PPIP5K2, TFR2, HNF4G, LRRC10B, PRC1 and FBXL20) and ten previously reported genes (INHBA, SMC2, ABO, PDX1, MTMR6, ACOT2, PGAP3, STARD3, GSDMB, ADAM33). MR provided support for a causal effect of PDAC on T2D using genetic instruments in the HNF4G and PDX1 loci, and unidirectional causality of VTE on PDAC involving the ABO locus (OR 2.12, P < 1e-7). No evidence of a causal effect of PDAC on VTE was found. INTERPRETATION These analyses identified candidate susceptibility genes and disease relationships for PDAC that warrant further investigation. HNF4G and PDX1 may induce PDAC-associated diabetes, whereas ABO may induce the causative effect of VTE on PDAC. FUNDING National Institutes of Health (USA).
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Affiliation(s)
- Marcus C B Tan
- Division of Surgical Oncology and Endocrine Surgery, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
| | - Chelsea A Isom
- Herbert Wertheim School of Public Health & Human Longevity Science, University of California, San Diego, San Diego, CA, USA
| | - Yangzi Liu
- Vanderbilt University School of Medicine, Nashville, TN, USA
| | | | - Lang Wu
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, Honolulu, HI, USA
| | - Dan Zhou
- School of Public Health and the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, China.
| | - Eric R Gamazon
- Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA; Clare Hall, University of Cambridge, Cambridge, United Kingdom.
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Satoh T, Nakatani E, Ariyasu H, Kawaguchi S, Ohno K, Itoh H, Hayashi K, Usui T. Pancreatic cancer risk in diabetic patients using the Japanese Regional Insurance Claims. Sci Rep 2024; 14:16958. [PMID: 39043788 PMCID: PMC11266625 DOI: 10.1038/s41598-024-67505-9] [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] [Received: 02/13/2024] [Accepted: 07/11/2024] [Indexed: 07/25/2024] Open
Abstract
Pancreatic cancer presents a critical health issue characterized by low survival rates. Identifying risk factors in specific populations, such as those with diabetes, is crucial for early detection and improved outcomes. This study aimed to identify risk factors for pancreatic cancer in diabetic patients using a longitudinal cohort from the Shizuoka Kokuho database, spanning April 2012 to September 2021. Diabetic patients were identified and monitored for the onset of pancreatic cancer. Factors analyzed included age, sex, the Elixhauser comorbidity index, and specific comorbidities. Statistical analyses involved univariate and multivariate Cox proportional hazards regression. The study identified 212,775 as diabetic patients and 1755 developed pancreatic cancer during the period. The annual incidence rate of pancreatic cancer in this group was 166.7 cases per 100,000 person-years. The study identified older age, male sex, a history of liver disease, chronic pancreatitis, and pancreatic cystic lesions as significant risk factors for pancreatic cancer in diabetic patients. The study also highlighted the absence of a significant association between diabetes type or diabetic complications and the onset of pancreatic cancer. These findings may aid in the early diagnosis of pancreatic cancer in diabetic patients and may inform revisions in screening practices in diabetic patients.
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Affiliation(s)
- Tatsunori Satoh
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
- Department of Gastroenterology, Shizuoka General Hospital, Shizuoka, Japan
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, 4-27-2 Kitaando, Aoi-Ku, Shizuoka, 420-0881, Japan
| | - Eiji Nakatani
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, 4-27-2 Kitaando, Aoi-Ku, Shizuoka, 420-0881, Japan.
| | - Hiroyuki Ariyasu
- Department of Diabetes and Endocrinology, Shizuoka General Hospital, Shizuoka, Japan
| | - Shinya Kawaguchi
- Department of Gastroenterology, Shizuoka General Hospital, Shizuoka, Japan
| | - Kazuya Ohno
- Department of Gastroenterology, Shizuoka General Hospital, Shizuoka, Japan
| | - Hiroshi Itoh
- Center for Preventive Medicine, Keio University, Tokyo, Japan
| | - Kaori Hayashi
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Takeshi Usui
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, 4-27-2 Kitaando, Aoi-Ku, Shizuoka, 420-0881, Japan
- Research Support Center, Shizuoka General Hospital, Shizuoka, Japan
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Pliszka M, Szablewski L. Associations between Diabetes Mellitus and Selected Cancers. Int J Mol Sci 2024; 25:7476. [PMID: 39000583 PMCID: PMC11242587 DOI: 10.3390/ijms25137476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 06/15/2024] [Accepted: 06/24/2024] [Indexed: 07/16/2024] Open
Abstract
Cancer is one of the major causes of mortality and is the second leading cause of death. Diabetes mellitus is a serious and growing problem worldwide, and its prevalence continues to grow; it is the 12th leading cause of death. An association between diabetes mellitus and cancer has been suggested for more than 100 years. Diabetes is a common disease diagnosed among patients with cancer, and evidence indicates that approximately 8-18% of patients with cancer have diabetes, with investigations suggesting an association between diabetes and some particular cancers, increasing the risk for developing cancers such as pancreatic, liver, colon, breast, stomach, and a few others. Breast and colorectal cancers have increased from 20% to 30% and there is a 97% increased risk of intrahepatic cholangiocarcinoma or endometrial cancer. On the other hand, a number of cancers and cancer therapies increase the risk of diabetes mellitus. Complications due to diabetes in patients with cancer may influence the choice of cancer therapy. Unfortunately, the mechanisms of the associations between diabetes mellitus and cancer are still unknown. The aim of this review is to summarize the association of diabetes mellitus with selected cancers and update the evidence on the underlying mechanisms of this association.
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Affiliation(s)
- Monika Pliszka
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chałubińskiego Str. 5, 02-004 Warsaw, Poland
| | - Leszek Szablewski
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chałubińskiego Str. 5, 02-004 Warsaw, Poland
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Ke TM, Lophatananon A, Muir KR. Strengthening the Evidence for a Causal Link between Type 2 Diabetes Mellitus and Pancreatic Cancer: Insights from Two-Sample and Multivariable Mendelian Randomization. Int J Mol Sci 2024; 25:4615. [PMID: 38731833 PMCID: PMC11082974 DOI: 10.3390/ijms25094615] [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: 03/20/2024] [Revised: 04/16/2024] [Accepted: 04/17/2024] [Indexed: 05/13/2024] Open
Abstract
This two-sample Mendelian randomization (MR) study was conducted to investigate the causal associations between type 2 diabetes mellitus (T2DM) and the risk of pancreatic cancer (PaCa), as this causal relationship remains inconclusive in existing MR studies. The selection of instrumental variables for T2DM was based on two genome-wide association study (GWAS) meta-analyses from European cohorts. Summary-level data for PaCa were extracted from the FinnGen and UK Biobank databases. Inverse variance weighted (IVW) and four other robust methods were employed in our MR analysis. Various sensitivity analyses and multivariable MR approaches were also performed to enhance the robustness of our findings. In the IVW and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analyses, the odds ratios (ORs) for each 1-unit increase in genetically predicted log odds of T2DM were approximately 1.13 for PaCa. The sensitivity tests and multivariable MR supported the causal link between T2DM and PaCa without pleiotropic effects. Therefore, our analyses suggest a causal relationship between T2DM and PaCa, shedding light on the potential pathophysiological mechanisms of T2DM's impact on PaCa. This finding underscores the importance of T2DM prevention as a strategy to reduce the risk of PaCa.
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Affiliation(s)
| | | | - Kenneth R. Muir
- Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PT, UK; (T.-M.K.); (A.L.)
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Conway RB, Hudson AG, Munro H, Fu D, McClain DA, Blot WJ. Diabetes and pancreatic cancer risk in a multiracial cohort. Diabet Med 2024; 41:e15234. [PMID: 37779225 PMCID: PMC11357321 DOI: 10.1111/dme.15234] [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: 03/17/2023] [Revised: 09/25/2023] [Accepted: 09/26/2023] [Indexed: 10/03/2023]
Abstract
AIMS To determine the relationship of diabetes with pancreatic cancer incidence among African American and Whites of similar socio-economic status. METHODS Using the Southern Community Cohort Study, we conducted a follow-up during 2002-2015 of pancreatic cancer incidence of 73,378 mostly low-income participants aged 40-79 years; 15,913 reported diabetes at baseline. Multivariable Cox analysis controlling for sex, family history of pancreatic cancer, BMI, smoking status, alcohol consumption, education, income and other important covariates, and with age as the timescale was used. RESULTS Totally, 265 incident pancreatic cancer cases were observed. Pancreatic cancer risk was increased among those with diabetes (HR 1.54, CI 1.16-2.05), with similar increases among African Americans (HR 1.51, CI 1.08-2.11) and Whites (HR 1.78, CI 1.00-3.16). No trend in risk was observed for diabetes duration among those with diabetes, with HRs of 1.39 (0.91-2.11), 2.31 (1.51-3.54) and 1.23 (0.80-1.89) for <5, 5-9 and 10+ years duration, respectively. African Americans were at increased risk of pancreatic cancer (HR = 1.40, 95% CI 1.05-1.87), which persisted after adjusting for diabetes (HR 1.36, CI 1.02-1.81). The effect sizes for other pancreatic cancer risk factors with pancreatic cancer were similar by diabetes status, although a stronger association with low BMI was evident among those with diabetes. CONCLUSIONS Diabetes increases pancreatic cancer risk similarly among African Americans and Whites in this Southern U.S. COHORT
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Affiliation(s)
- Rebecca B.N. Conway
- American Academy of Epidemiology, Inc., 2008 S. Wiley Avenue, Tyler, TX 75701, USA
- Department of Epidemiology, University of Colorado School of Public Health, Anschutz Medical Campus, 13001 East 17th Place, Mail Stop B119 Aurora, CO, 80045, USA
| | - Alana G. Hudson
- Public Health Strategies, LLC, 515 Highland Avenue, South Charleston, WV, 25303, USA
| | - Heather Munro
- Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, 2525 West End Avenue Nashville, TN, 37203
| | - David Fu
- Cancer Center, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong St., Wuchang District, Wuhan City, Hubei Province, 430060, P.R. China
| | - Donald A. McClain
- Section of Endocrinology and Metabolism, Wake Forest School of Medicine, 475 Vine St, Winston-Salem, NC, 27157, USA
| | - William J. Blot
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, 2525 West Avenue, Nashville, TN, 27203, USA
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8
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Szablewski L. Insulin Resistance: The Increased Risk of Cancers. Curr Oncol 2024; 31:998-1027. [PMID: 38392069 PMCID: PMC10888119 DOI: 10.3390/curroncol31020075] [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] [Received: 11/24/2023] [Revised: 01/15/2024] [Accepted: 02/10/2024] [Indexed: 02/24/2024] Open
Abstract
Insulin resistance, also known as impaired insulin sensitivity, is the result of a decreased reaction of insulin signaling to blood glucose levels. This state is observed when muscle cells, adipose tissue, and liver cells, improperly respond to a particular concentration of insulin. Insulin resistance and related increased plasma insulin levels (hyperinsulinemia) may cause metabolic impairments, which are pathological states observed in obesity and type 2 diabetes mellitus. Observations of cancer patients confirm that hyperinsulinemia is a major factor influencing obesity, type 2 diabetes, and cancer. Obesity and diabetes have been reported as risks of the initiation, progression, and metastasis of several cancers. However, both of the aforementioned pathologies may independently and additionally increase the cancer risk. The state of metabolic disorders observed in cancer patients is associated with poor outcomes of cancer treatment. For example, patients suffering from metabolic disorders have higher cancer recurrence rates and their overall survival is reduced. In these associations between insulin resistance and cancer risk, an overview of the various pathogenic mechanisms that play a role in the development of cancer is discussed.
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Affiliation(s)
- Leszek Szablewski
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chałubińskiego 5 Str., 02-004 Warsaw, Poland
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Ali S, Coory M, Donovan P, Na R, Pandeya N, Pearson SA, Spilsbury K, Stewart LM, Thompson B, Tuesley K, Waterhouse M, Webb PM, Jordan SJ, Neale RE. Association between unstable diabetes mellitus and risk of pancreatic cancer. Pancreatology 2024; 24:66-72. [PMID: 38000983 DOI: 10.1016/j.pan.2023.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 10/29/2023] [Accepted: 11/13/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND Deterioration of glycaemic control in people with long-standing diabetes mellitus (diabetes) may be a possible indicator of pancreatic cancer. However, the magnitude of the association between diabetes deterioration and pancreatic cancer has received little attention. METHODS We conducted a matched cohort study, nested within a population-based cohort of Australian women with diabetes. Women with unstable diabetes, defined as a change in medication after a 2-year period of stable medication use, were matched by birth year to those with stable diabetes, in a 1:4 ratio. We used flexible parametric survival models to estimate hazard ratios (HRs) and 95% confidence intervals (CI). RESULTS We included 134,954 and 539,789 women in the unstable and stable diabetes cohorts, respectively (mean age 68 years). In total, 1,315 pancreatic cancers were diagnosed. Deterioration of stable diabetes was associated with a 2.5-fold increased risk of pancreatic cancer (HR 2.55; 95% CI 2.29-2.85). The risk was particularly high within the first year after diabetes deteriorated. HRs at 3 months, 6 months and 1 year were: 5.76 (95% CI 4.72-7.04); 4.56 (95% CI 3.81-5.46); and 3.33 (95% CI 2.86-3.89), respectively. The risk was no longer significantly different after 7 years. CONCLUSIONS Deterioration in glycaemic control in people with previously stable diabetes may be an indicator of pancreatic cancer, suggesting investigations of the pancreas may be appropriate. The weaker longer-term (3-7 years) association between diabetes deterioration and pancreatic cancer may indicate that poor glycaemic control can be a risk factor for pancreatic cancer.
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Affiliation(s)
- Sitwat Ali
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; School of Public Health, University of Queensland, Brisbane, QLD, Australia
| | - Michael Coory
- Centre of Research Excellence in Stillbirth, Mater Research Institute, The University of Queensland, Brisbane, Queensland, Australia
| | - Peter Donovan
- Royal Brisbane and Women's Hospital, Australia; Faculty of Medicine, The University of Queensland, Australia
| | - Renhua Na
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Nirmala Pandeya
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | | | - Katrina Spilsbury
- Centre Institute for Health Research, University of Notre Dame Australia, Fremantle, Western Australia, Australia
| | - Louise M Stewart
- School of Population and Global Health, The University of Western Australia, Crawley, Western Australia, Australia
| | - Bridie Thompson
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Karen Tuesley
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; School of Public Health, University of Queensland, Brisbane, QLD, Australia
| | - Mary Waterhouse
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Penelope M Webb
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; School of Public Health, University of Queensland, Brisbane, QLD, Australia
| | - Susan J Jordan
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; School of Public Health, University of Queensland, Brisbane, QLD, Australia
| | - Rachel E Neale
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; School of Public Health, University of Queensland, Brisbane, QLD, Australia.
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10
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Zheng CY, Zhong W, Xu JH, Yuan YH, Chen NZ, Liang WL, Chen QK, Lai Y. Correlation between High Incidence of Colorectal Neoplastic Polyps and High-risk Adenomas in Patients with Diabetes Mellitus: A Retrospective Study. Endocr Metab Immune Disord Drug Targets 2024; 24:1110-1119. [PMID: 37711116 DOI: 10.2174/1871530323666230913105743] [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: 03/01/2023] [Revised: 07/26/2023] [Accepted: 07/28/2023] [Indexed: 09/16/2023]
Abstract
BACKGROUND Early detection and resection of colorectal polyps by routine colonoscopy screening can be effective in reducing the risk of colorectal cancer (CRC). OBJECTIVE This study aimed to determine the association between diabetes mellitus (DM) and different types of colorectal polyps in the Chinese population. METHODS A retrospective analysis was performed on inpatients admitted to the Gastroenterology Department of our hospital from January to December 2019. Clinical data, and colonoscopy and pathology findings of the subjects were collected. Bivariate analysis was used to assess factors associated with colorectal polyps. Significant variables from the bivariate evaluation were included in a stepwise multivariate logistic regression analysis to recognize independent predictors of neoplastic polyps and high-risk adenomas. RESULTS The proportion of patients with DM was significantly higher in patients with neoplastic polyps and high-risk adenomas than in patients without polyps. Age ≥ 50 years, male gender, and a first-degree relative with a history of CRC were independent risk factors for neoplastic polyps and high-risk adenomas, even in non-smokers. An independent risk factor analysis that did not include a family history of CRC showed that age, gender, and alcohol consumption were independent risk factors for neoplastic polyps and high-risk adenomas. DM was an independent risk factor for high-risk adenomas (OR = 2.902, 95% CI = 1.221-6.899; p = 0.016) after adjusting for age, gender, alcohol consumption, and body mass index. Thus, a history of DM significantly increases the risk of high-risk adenomas. CONCLUSION This study demonstrated that patients with DM, age ≥ 50 years, male gender, alcohol consumption, and a first-degree relative with a history of CRC should undergo regular endoscopic screening and colonic polypectomy.
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Affiliation(s)
- Chuan-Yu Zheng
- Department of Gastroenterology, The Second People's Hospital of Foshan, Foshan, China
| | - Wa Zhong
- Department of Gastroenterology, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Guangzhou, China
| | - Ji-Hao Xu
- Department of Gastroenterology, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Guangzhou, China
| | - Yu-Hong Yuan
- Department of Gastroenterology, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Guangzhou, China
| | - Nai-Zhao Chen
- Department of Gastroenterology, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Guangzhou, China
| | - Wei-Ling Liang
- Department of Gastroenterology, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Guangzhou, China
| | - Qi-Kui Chen
- Department of Gastroenterology, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Guangzhou, China
| | - Yu Lai
- Department of Gastroenterology, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Guangzhou, China
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Fontvieille E, Viallon V, Recalde M, Cordova R, Jansana A, Peruchet-Noray L, Lennon H, Heath AK, Aune D, Christakoudi S, Katzke V, Kaaks R, Inan-Eroglu E, Schulze MB, Mellemkjær L, Tjønneland A, Overvad K, Farràs M, Petrova D, Amiano P, Chirlaque MD, Moreno-Iribas C, Tin Tin S, Masala G, Sieri S, Ricceri F, Panico S, May AM, Monninkhof EM, Weiderpass E, Gunter MJ, Ferrari P, Freisling H. Body mass index and cancer risk among adults with and without cardiometabolic diseases: evidence from the EPIC and UK Biobank prospective cohort studies. BMC Med 2023; 21:418. [PMID: 37993940 PMCID: PMC10666332 DOI: 10.1186/s12916-023-03114-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 10/16/2023] [Indexed: 11/24/2023] Open
Abstract
BACKGROUND Whether cancer risk associated with a higher body mass index (BMI), a surrogate measure of adiposity, differs among adults with and without cardiovascular diseases (CVD) and/or type 2 diabetes (T2D) is unclear. The primary aim of this study was to evaluate separate and joint associations of BMI and CVD/T2D with the risk of cancer. METHODS This is an individual participant data meta-analysis of two prospective cohort studies, the UK Biobank (UKB) and the European Prospective Investigation into Cancer and nutrition (EPIC), with a total of 577,343 adults, free of cancer, T2D, and CVD at recruitment. We used Cox proportional hazard regressions to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between BMI and incidence of obesity-related cancer and in turn overall cancer with a multiplicative interaction between BMI and the two cardiometabolic diseases (CMD). HRs and 95% CIs for separate and joint associations for categories of overweight/obesity and CMD status were estimated, and additive interaction was quantified through relative excess risk due to interaction (RERI). RESULTS In the meta-analysis of both cohorts, BMI (per ~ 5 kg/m2) was positively associated with the risk of obesity-related cancer among participants without a CMD (HR: 1.11, 95%CI: 1.07,1.16), among participants with T2D (HR: 1.11, 95% CI: 1.05,1.18), among participants with CVD (HR: 1.17, 95% CI: 1.11,1.24), and suggestively positive among those with both T2D and CVD (HR: 1.09, 95% CI: 0.94,1.25). An additive interaction between obesity (BMI ≥ 30 kg/m2) and CVD with the risk of overall cancer translated into a meta-analytical RERI of 0.28 (95% CI: 0.09-0.47). CONCLUSIONS Irrespective of CMD status, higher BMI increased the risk of obesity-related cancer among European adults. The additive interaction between obesity and CVD suggests that obesity prevention would translate into a greater cancer risk reduction among population groups with CVD than among the general population.
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Affiliation(s)
- Emma Fontvieille
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO), 25 Avenue Tony Garnier, CS 90627, 69366, Lyon, CEDEX 07, France
| | - Vivian Viallon
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO), 25 Avenue Tony Garnier, CS 90627, 69366, Lyon, CEDEX 07, France
| | - Martina Recalde
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO), 25 Avenue Tony Garnier, CS 90627, 69366, Lyon, CEDEX 07, France
| | - Reynalda Cordova
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO), 25 Avenue Tony Garnier, CS 90627, 69366, Lyon, CEDEX 07, France
| | - Anna Jansana
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO), 25 Avenue Tony Garnier, CS 90627, 69366, Lyon, CEDEX 07, France
| | - Laia Peruchet-Noray
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO), 25 Avenue Tony Garnier, CS 90627, 69366, Lyon, CEDEX 07, France
- Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Hannah Lennon
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO), 25 Avenue Tony Garnier, CS 90627, 69366, Lyon, CEDEX 07, France
| | - Alicia K Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Dagfinn Aune
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Department of Nutrition, Oslo New University College, Oslo, Norway
- Department of Research, Cancer Registry of Norway, Oslo, Norway
| | - Sofia Christakoudi
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Verena Katzke
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rudolf Kaaks
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Elif Inan-Eroglu
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Matthias B Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
- Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
| | | | - Anne Tjønneland
- Danish Cancer Society Research Center, Copenhagen, Denmark
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Kim Overvad
- Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Marta Farràs
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Institut Català d'Oncologia, Bellvitge Biomedical Research Institute (IDIBELL), 08908, L'Hospitalet de Llobregat, Spain
| | - Dafina Petrova
- Escuela Andaluza de Salud Pública (EASP), 18011, Granada, Spain
- Instituto de Investigación Biosanitaria Ibs.GRANADA, 18012, Granada, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain
| | - Pilar Amiano
- Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, 2013, San Sebastian, Spain
- Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, 20014, San Sebastián, Spain
- Spanish Consortium for Research On Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain
| | - María-Dolores Chirlaque
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain
- Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain
| | - Conchi Moreno-Iribas
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain
- Navarra Public Health Institute, Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
| | - Sandar Tin Tin
- Cancer Epidemiology Unit, Oxford Population Health, University of Oxford, Oxford, UK
| | - Giovanna Masala
- Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy
| | - Sabina Sieri
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori Di Milano, Milan, Italy
| | - Fulvio Ricceri
- Department of Clinical and Biological Sciences, Centre for Biostatistics, Epidemiology, and Public Health, University of Turin, Turin, Italy
| | - Salvatore Panico
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Anne M May
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Evelyn M Monninkhof
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Elisabete Weiderpass
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO), 25 Avenue Tony Garnier, CS 90627, 69366, Lyon, CEDEX 07, France
| | - Marc J Gunter
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO), 25 Avenue Tony Garnier, CS 90627, 69366, Lyon, CEDEX 07, France
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Pietro Ferrari
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO), 25 Avenue Tony Garnier, CS 90627, 69366, Lyon, CEDEX 07, France
| | - Heinz Freisling
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO), 25 Avenue Tony Garnier, CS 90627, 69366, Lyon, CEDEX 07, France.
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12
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Lee HS, Chae W, Sung MJ, Keum J, Jo JH, Chung MJ, Park JY, Park SW, Song SY, Park EC, Nam CM, Jang SI, Bang S. Difference of risk of pancreatic cancer in new-onset diabetes and long-standing diabetes: population-based cohort study. J Clin Endocrinol Metab 2022; 108:1338-1347. [PMID: 36548964 DOI: 10.1210/clinem/dgac728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 12/09/2022] [Accepted: 12/12/2022] [Indexed: 12/24/2022]
Abstract
CONTEXT Considering the absence of methods to find pancreatic cancer early, surveillance of high-risk groups is needed for early diagnosis. OBJECTIVE The study aimed to investigate the effect in the incidence of pancreatic cancer and the differences between new-onset DM (NODM) and long-standing DM (LSDM) since NODM group is a representative high-risk group. METHODS The Korean National Health Insurance Service-National Sample Cohort between 2002 and 2013 data was used. Regarding 88,396 people with DM (case group), we conducted a 1:1 propensity score matching to select a matched non-DM population (control group). To investigate the interaction between DM and the time variable distinguishing NODM and LSDM, we performed a multi-variable time-dependent Cox regression analysis. RESULTS The incidence of pancreatic cancer was higher in the DM group compared to the non-DM group (0.52% vs. 0.16%, P < 0.001). The DM group had shown different risk of pancreatic cancer development according to the duration since the DM diagnosis (NODM hazard ratio (HR): 3.81, 95% confidence interval (CI): 2.97-4.88, P < 0.001; LSDM HR: 1.53, 95% CI: 1.11-2.11, P < 0.001). When the NODM and the LSDM groups were compared, the risk of pancreatic cancer was higher in the NODM group than LSDM group (HR: 1.55, P = 0.020). In subgroup analysis, NODM group showed that men (HR = 4.42 95% CI: 3.15-6.19, P < 0.001) and patients who were in their 50 s (HR = 7.54, 95% CI: 3.24-17.56, P < 0.001) were at a higher risk of developing pancreatic cancer than matched same sex or age control group (non-DM population), respectively. CONCLUSION The risk of pancreatic cancer was greater in people with DM than non-DM population. Among people with DM, NODM showed a higher risk of pancreatic cancer than long standing DM.
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Affiliation(s)
- Hee Seung Lee
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Wonjeong Chae
- Department of Health Policy and Management, Yonsei University Graduate School of Public Health, Seoul, Republic of Korea
- Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea
| | - Min Je Sung
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jiyoung Keum
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jung Hyun Jo
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Moon Jae Chung
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jeong Youp Park
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung Woo Park
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Si Young Song
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Eun-Cheol Park
- Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea
- Department of Preventive Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Chung Mo Nam
- Department of Preventive Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea
- Department of Biostatics, College of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Sung-In Jang
- Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea
- Department of Preventive Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Seungmin Bang
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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13
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Ali S, Na R, Tuesley K, Spilsbury K, Stewart LM, Coory M, Webb PM, Donovan P, Pearson SA, Jordan SJ, Neale RE. The association between diabetes mellitus of different durations and risk of pancreatic cancer: an Australian national data-linkage study in women. Cancer Epidemiol 2022; 81:102266. [PMID: 36240705 DOI: 10.1016/j.canep.2022.102266] [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: 05/27/2022] [Revised: 08/29/2022] [Accepted: 09/19/2022] [Indexed: 11/02/2022]
Abstract
AIMS The bidirectional association between diabetes mellitus (DM) and pancreatic cancer (PC) is established; however, the strength of association between duration of DM and risk of PC needs further investigation. METHODS We conducted a case-control study nested within a population-based cohort of Australian women established using record linkage. Women diagnosed with PC from July 2007 to December 2013, were matched to five controls based on age and state of residence. DM was defined according to prescription of anti-diabetic medication from administrative prescription data. We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI), adjusted for area-level socioeconomic status, rurality of residence, weighted comorbidity score, and predicted probability of obesity. RESULTS The analyses included 7,267 cases and 35,978 controls. The mean age at the time of DM diagnosis was 71 years whereas the mean age at the time of diagnosis of PC was 76 years. A history of DM of any duration was associated with a 2-fold increase in risk of PC (OR=2.12; 95%CI:1.96-2.29) compared to having no history of DM. The risk decreased with increasing duration of DM. The highest risk was in those who had recent-onset DM (OR=8.08; 95%CI:6.88-9.50 for <12 months of DM), but the risk remained elevated with ≥5 years of DM (OR=1.40; 95%CI:1.27-1.55). CONCLUSION The markedly increased risk of PC in those with recent-onset DM emphasises the need for further research to distinguish patients for whom new-onset DM is a manifestation of PC from those with type-2 DM. The elevated risk associated with long-standing DM suggests that preventing DM may contribute to a reduction in the incidence of PC.
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Affiliation(s)
- Sitwat Ali
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Public Health, University of Queensland, Brisbane, Queensland, Australia
| | - Renhua Na
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - Karen Tuesley
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Public Health, University of Queensland, Brisbane, Queensland, Australia
| | - Katrina Spilsbury
- Centre for Health Research, University of Notre Dame Australia, Fremantle, Western Australia, Australia
| | - Louise M Stewart
- School of Population and Global Health, The University of Western Australia, Crawley, Western Australia, Australia
| | - Michael Coory
- Centre of Research Excellence in Stillbirth, Mater Research Institute, The University of Queensland, Brisbane, Queensland, Australia
| | - Penelope M Webb
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Public Health, University of Queensland, Brisbane, Queensland, Australia
| | - Peter Donovan
- Royal Brisbane and Women's Hospital, Australia; Faculty of Medicine, The University of Queensland, Australia
| | - Sallie-Anne Pearson
- Centre for Big Data Research in Health, University of New South Wales UNSW, Sydney, New South Wales, Australia
| | - Susan J Jordan
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Public Health, University of Queensland, Brisbane, Queensland, Australia
| | - Rachel E Neale
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Public Health, University of Queensland, Brisbane, Queensland, Australia.
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14
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Mukherjee AG, Wanjari UR, Gopalakrishnan AV, Bradu P, Sukumar A, Patil M, Renu K, Dey A, Vellingiri B, George A, Ganesan R. Implications of cancer stem cells in diabetes and pancreatic cancer. Life Sci 2022; 312:121211. [PMID: 36414089 DOI: 10.1016/j.lfs.2022.121211] [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: 08/23/2022] [Revised: 11/15/2022] [Accepted: 11/16/2022] [Indexed: 11/21/2022]
Abstract
This review provides a detailed study of pancreatic cancer (PC) and the implication of different types of cancers concerning diabetes. The combination of anti-diabetic drugs with other anti-cancer drugs and phytochemicals can help prevent and treat this disease. PC cancer stem cells (CSCs) and how they migrate and develop into malignant tumors are discussed. A detailed explanation of the different mechanisms of diabetes development, which can enhance the pancreatic CSCs' proliferation by increasing the IGF factor levels, epigenetic modifications, DNA damage, and the influence of lifestyle factors like obesity, and inflammation, has been discussed. It also explains how cancer due to diabetes is associated with high mortality rates. One of the well-known diabetic drugs, metformin, can be combined with other anti-cancer drugs and prevent the development of PC and has been taken as one of the prime focus in this review. Overall, this paper provides insight into the relationship between diabetes and PC and the methods that can be employed to diagnose this disease at an earlier stage successfully.
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Affiliation(s)
- Anirban Goutam Mukherjee
- Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Uddesh Ramesh Wanjari
- Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Abilash Valsala Gopalakrishnan
- Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India.
| | - Pragya Bradu
- Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Aarthi Sukumar
- Department of Integrative Biology, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India
| | - Megha Patil
- Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Kaviyarasi Renu
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600077, Tamil Nadu, India
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, Kolkata, West Bengal, 700073, India
| | - Balachandar Vellingiri
- Stem cell and Regenerative Medicine/Translational Research, Department of Zoology, School of Basic Sciences, Central University of Punjab (CUPB), Bathinda - 151401, Punjab, India
| | - Alex George
- Jubilee Centre for Medical Research, Jubilee Mission Medical College and Research Institute, Thrissur, 680005, Kerala, India
| | - Raja Ganesan
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, 24252, Republic of Korea
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15
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Ke TM, Lophatananon A, Muir KR. Risk Factors Associated with Pancreatic Cancer in the UK Biobank Cohort. Cancers (Basel) 2022; 14:cancers14204991. [PMID: 36291775 PMCID: PMC9599736 DOI: 10.3390/cancers14204991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 09/16/2022] [Accepted: 10/10/2022] [Indexed: 01/18/2023] Open
Abstract
Evidence on pancreatic cancer (PaCa) risk factors from large population-based cohort studies is limited. This study investigated the PaCa risk factors and the population attributable fraction (PAF) of modifiable risk factors in the UK Biobank cohort. The UK Biobank is a prospective cohort consisting of 502,413 participants with a mean follow-up time of 8.2 years. A binomial generalized linear regression model was used to calculate relative risks for PaCa risk factors. PAF was calculated to estimate the proportional reduction in PaCa if modifiable risk factors were to be eliminated. A total of 728 (0.14%) PaCa incident cases and 412,922 (82.19%) non-PaCa controls were analyzed. The non-modifiable risk factors included age and gender. The modifiable risk factors were cigarette smoking, overweight and obesity, increased waist circumstance, abdominal obesity, Diabetic Mellitus (DM), and pancreatitis history. The PAF suggested that eliminating smoking and obesity can contribute around a 16% reduction in PaCa cases while avoiding abdominal obesity can eliminate PaCa cases by 22%. Preventing pancreatitis and DM could potentially reduce PaCa cases by 1% and 6%, respectively. This study has identified modifiable and non-modifiable PaCa risk factors in the UK population. The PAF of modifiable risk factors can be applied to inform PaCa prevention programs.
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16
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Chan RNC, Lee TTL, Chou OHI, So J, Chung CT, Dee EC, Ng K, Tang P, Roever L, Liu T, Wong WT, Tse G, Lee S. Risk Factors of Pancreatic Cancer in Patients With Type 2 Diabetes Mellitus: The Hong Kong Diabetes Study. J Endocr Soc 2022; 6:bvac138. [PMID: 36267596 PMCID: PMC9562787 DOI: 10.1210/jendso/bvac138] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Indexed: 11/19/2022] Open
Abstract
CONTEXT Diabetes mellitus (DM) is associated with the development of pancreatic cancer (PaC), but few large-scale studies have examined its predictive risk factors. OBJECTIVE The present study aims to examine the predictors for PaC in patients with type 2 diabetes mellitus (T2DM) in a territory-wide, retrospective cohort study. METHODS This was a territory-wide, retrospective cohort study of patients with T2DM mellitus older than 40 years with no prior history of PaC. Baseline demographics, use of antidiabetic medications, comorbidities, and biochemical parameters were extracted. Cox regression was used to calculate hazard ratios (HR) with 95% CI. Subgroup analyses based on chronic kidney disease (CKD) stages were performed. RESULTS This study consisted of 273 738 patients (age = 65.4 ± 12.7 years, male = 48.2%, follow-up duration = 3547 ± 1207 days, disease duration = 4.8 ± 2.3 years), of whom 1148 developed PaC. The number of antidiabetic medications prescribed (HR: 1.20; 95% CI, 1.01-1.42; P = .040), diabetic microvascular complications (HR: 1.91; 95% CI, 1.30-2.81; P < .001), chronic kidney disease (HR: 1.81; 95% CI, 1.25-2.64; P = .002), use of acarbose (HR: 2.24; 95% CI, 1.35-3.74; P = .002), and use of glucagon-like peptide-1 receptor agonist (HR: 4.00; 95% CI: 1.28-12.53, P = .017) were associated with PaC development on multivariable Cox regression adjusting for the duration of DM, mean glycated hemoglobin A1c, and history of pancreatic diseases. Stage 3A CKD or below was associated with PaC but not stage 3B or beyond. CONCLUSION Diabetic microvascular complications, especially stage 1, 2, and 3A CKD, were associated with PaCs.
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Affiliation(s)
- Raymond Ngai Chiu Chan
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
| | - Teddy Tai Loy Lee
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
| | - Oscar Hou In Chou
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
| | - Jenny So
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
| | - Cheuk To Chung
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
| | - Edward Christopher Dee
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Kenrick Ng
- Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Pias Tang
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
| | - Leonardo Roever
- Department of Clinical Research, Federal University of Uberlandia, Uberlandia, Brazil
| | - Tong Liu
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Wing Tak Wong
- School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Gary Tse
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
- Kent and Medway Medical School, University of Kent and Canterbury Christ Church University, Canterbury, CT2 7NT, UK
| | - Sharen Lee
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
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17
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Dong WW, Zhang DL, Wang ZH, Lv CZ, Zhang P, Zhang H. Different types of diabetes mellitus and risk of thyroid cancer: A meta-analysis of cohort studies. Front Endocrinol (Lausanne) 2022; 13:971213. [PMID: 36213272 PMCID: PMC9537385 DOI: 10.3389/fendo.2022.971213] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 09/05/2022] [Indexed: 11/30/2022] Open
Abstract
Objective Sex-specific thyroid cancer risk exists in patients diagnosed with diabetes mellitus (DM). However, thyroid cancer risk in different types of DM is still unclear. This meta-analysis aims to identify the real correlation between different types of DM and thyroid cancer risk in both sexes. Methods Studies were identified by an electronic search of PubMed, EMBASE, and Cochrane Library on 16 January 2022. A random-effects model was used to estimate the relative risks (RRs). The Cochran's Q and I2 statistics were computed to detect heterogeneity between studies. Results In comparison with non-DM counterparts, patients with DM had a 1.32-fold higher risk of thyroid cancer (95% CI, 1.22-1.44) with 1.26-fold (95% CI, 1.12-1.41) in men and 1.36-fold (95% CI, 1.22-1.52) in women, respectively. Subgroup analysis by the type of DM showed that the RR of thyroid cancer in patients with type 2 diabetes was 1.34 (95% CI, 1.17-1.53) in the study population with 1.32 (95% CI, 1.12-1.54) in men and 1.37 (95% CI, 1.12-1.68) in women, respectively; the RR of thyroid cancer was 1.30 (95% CI, 1.17-1.43) in patients with gestational diabetes; the risk of thyroid cancer in patients with type 1 diabetes was 1.51-fold in women but not in men. Although there were some heterogeneities, it did not affect the above results of this study. Conclusion This study indicates that, compared with non-DM individuals, patients with any type of DM have an elevated thyroid cancer risk. This positive correlation between type 2 diabetes and thyroid cancer risk exists in both men and women. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, CRD42022304028.
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Affiliation(s)
| | | | | | | | | | - Hao Zhang
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, China
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Yang Q, Zhang J, Zhu Y. Potential Roles of the Gut Microbiota in Pancreatic Carcinogenesis and Therapeutics. Front Cell Infect Microbiol 2022; 12:872019. [PMID: 35463649 PMCID: PMC9019584 DOI: 10.3389/fcimb.2022.872019] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 03/14/2022] [Indexed: 11/28/2022] Open
Abstract
The intestinal microenvironment is composed of normal gut microbiota and the environment in which it lives. The largest microecosystem in the human body is the gut microbiota, which is closely related to various diseases of the human body. Pancreatic cancer (PC) is a common malignancy of the digestive system worldwide, and it has a 5-year survival rate of only 5%. Early diagnosis of pancreatic cancer is difficult, so most patients have missed their best opportunity for surgery at the time of diagnosis. However, the etiology is not entirely clear, but there are certain associations between PC and diet, lifestyle, obesity, diabetes and chronic pancreatitis. Many studies have shown that the translocation of the gut microbiota, microbiota dysbiosis, imbalance of the oral microbiota, the interference of normal metabolism function and toxic metabolite products are closely associated with the incidence of PC and influence its prognosis. Therefore, understanding the correlation between the gut microbiota and PC could aid the diagnosis and treatment of PC. Here, we review the correlation between the gut microbiota and PC and the research progresses for the gut microbiota in the diagnosis and treatment of PC.
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Affiliation(s)
- Qiaoyu Yang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China
- Queen Mary College, Nanchang University, Nanchang, China
| | - Jihang Zhang
- Institute of Cardiovascular Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Yin Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China
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19
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Hu Y, Zeng N, Ge Y, Wang D, Qin X, Zhang W, Jiang F, Liu Y. Identification of the Shared Gene Signatures and Biological Mechanism in Type 2 Diabetes and Pancreatic Cancer. Front Endocrinol (Lausanne) 2022; 13:847760. [PMID: 35432196 PMCID: PMC9010232 DOI: 10.3389/fendo.2022.847760] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 02/24/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The relationship between pancreatic cancer (PC) and type 2 diabetes mellitus (T2DM) has long been widely recognized, but the interaction mechanisms are still unknown. This study was aimed to investigate the shared gene signatures and molecular processes between PC and T2DM. METHODS The Gene Expression Omnibus (GEO) database was used to retrieve the RNA sequence and patient information of PC and T2DM. Weighted gene co-expression network analysis (WGCNA) was performed to discover a co-expression network associated with PC and T2DM. Enrichment analysis of shared genes present in PC and T2DM was performed by ClueGO software. These results were validated in the other four cohorts based on differential gene analysis. The predictive significance of S100A6 in PC was evaluated using univariate and multivariate Cox analyses, as well as Kaplan-Meier plots. The biological process of S100A6 enrichment in PC was detected using Gene Set Enrichment Analysis (GSEA). The involvement of S100A6 in the tumor immune microenvironment (TIME) was assessed by CIBERSORT. In vitro assays were used to further confirm the function of S100A6 in PC. RESULTS WGCNA recognized three major modules for T2DM and two major modules for PC. There were 44 shared genes identified for PC and T2DM, and Gene Ontology (GO) analysis showed that regulation of endodermal cell fate specification was primarily enriched. In addition, a key shared gene S100A6 was derived in the validation tests. S100A6 was shown to be highly expressed in PC compared to non-tumor tissues. PC patients with high S100A6 expression had worse overall survival (OS) than those with low expression. GSEA revealed that S100A6 is involved in cancer-related pathways and glycometabolism-related pathways. There is a strong relationship between S100A6 and TIME. In vitro functional assays showed that S100A6 helped to induce the PC cells' proliferation and migration. We also proposed a diagram of common mechanisms of PC and T2DM. CONCLUSIONS This study firstly revealed that the regulation of endodermal cell fate specification may be common pathogenesis of PC and T2DM and identified S100A6 as a possible biomarker and therapeutic target for PC and T2DM patients.
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Affiliation(s)
- Yifang Hu
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ni Zeng
- Department of Dermatology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yaoqi Ge
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dan Wang
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaoxuan Qin
- Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wensong Zhang
- Department of Pharmacy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Feng Jiang
- Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Yun Liu
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
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20
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Wang X, Xu W, Hu X, Yang X, Zhang M. The Prognostic Role of Glycemia in Patients With Pancreatic Carcinoma: A Systematic Review and Meta-Analysis. Front Oncol 2022; 12:780909. [PMID: 35223469 PMCID: PMC8866248 DOI: 10.3389/fonc.2022.780909] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 01/03/2022] [Indexed: 12/14/2022] Open
Abstract
Background Fasting blood glucose and glycated hemoglobin (HbA1c) levels are associated with the risk of pancreatic cancer. Aim To examine the relationship between perioperative glucose and HbA1c levels and prognosis in patients with pancreatic cancer. Methods PubMed, Embase, and the Cochrane Library were queried for potentially eligible studies published up to May 2021. The exposures were perioperative fasting glucose and HbA1c levels. The primary outcome was survival. The secondary outcome was complications. All analyses were performed using the random-effects model. Results Ten studies (48,424 patients) were included. The pre-operative (HR=1.10, 95%CI: 0.89-1.35; I2 = 45.1%, Pheterogeneity=0.078) and postoperative (HR=1.19, 95%CI: 0.92-1.54; I2 = 67.9%, Pheterogeneity=0.001) blood glucose levels were not associated with the survival to pancreatic cancer. Similar results were observed for HbA1c (HR=1.09, 95%CI: 0.75-1.58; I2 = 64.2%, Pheterogeneity=0.039), fasting blood glucose (FBG)/HbA1c (HR=1.16, 95%CI: 0.67-1.68; I2 = 0.0%, Pheterogeneity=0.928), and FBG (HR=1.75, 95%CI: 0.81-3.75; I2 = 79.4%, Pheterogeneity=0.008). Pre-operative blood glucose levels were not associated with postoperative complications (OR=0.90, 95%CI: 0.52-1.56), but postoperative glucose levels were associated with postoperative complications (OR=3.06, 95%CI: 1.88-4.97; I2 = 0.0%, Pheterogeneity=0.619). Conclusion Blood glucose, FBG, and HbA1c levels are not associated with the survival of patients with pancreatic cancer. Postoperative blood glucose levels could predict postoperative complications.
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Affiliation(s)
- Xiaofang Wang
- Department of Clinical Oncology and Department of Hospice Care, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wanfeng Xu
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiaoru Hu
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xianghong Yang
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Mingming Zhang
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
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21
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Impact of diabetes mellitus on long-term prognosis after gastrectomy for advanced gastric cancer: a propensity score matching analysis. Surg Today 2022; 52:1382-1391. [DOI: 10.1007/s00595-022-02482-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 12/27/2021] [Indexed: 12/24/2022]
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22
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Winarni D, Husna FN, Syadzha MF, Susilo RJK, Hayaza S, Ansori ANM, Alamsjah MA, Amin MNG, Wulandari PAC, Pudjiastuti P, Awang K. Topical Administration Effect of Sargassum duplicatum and Garcinia mangostana Extracts Combination on Open Wound Healing Process in Diabetic Mice. SCIENTIFICA 2022; 2022:9700794. [PMID: 35186344 PMCID: PMC8850046 DOI: 10.1155/2022/9700794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 12/20/2021] [Accepted: 01/13/2022] [Indexed: 05/14/2023]
Abstract
This research aimed to determine the topical administration effect of the combination of Sargassum duplicatum and Garcinia mangostana extracts to ameliorate diabetic open wound healing. The study used 24 adult males of Mus musculus (BALB/c strain, 3-4 months, 30-40 g). They were divided into normal control groups (KN) and diabetic groups. The diabetic group was streptozotocin-induced and divided further into three treatment groups: the diabetic control group (KD), the S. duplicatum treatment group (PA), and the combination of S. duplicatum and G. mangostana treatment group (PAM). The dose of treatment was 50 mg/kg of body weight. Each group was divided into three treatment durations, which were 3 days, 7 days, and 14 days. The wound healing process was determined by wound width, the number of neutrophils, macrophages, fibroblasts, fibrocytes, and collagen density. Histological observation showed that the topical administration of combination extracts increased the re-epithelialization of the wounded area, fibroblasts, fibrocytes, and collagen synthesis. The topical administration of combination extracts also decreased the number of neutrophils and macrophages. This study concluded that the topical administration of the combination of S. duplicatum and G. mangostana extracts improved the open wound healing process in diabetic mice.
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Affiliation(s)
- Dwi Winarni
- Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya 60115, Indonesia
| | - Fitria Nikmatul Husna
- Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya 60115, Indonesia
| | - Muhammad Farraz Syadzha
- Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya 60115, Indonesia
| | | | - Suhailah Hayaza
- Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya 60115, Indonesia
| | - Arif Nur Muhammad Ansori
- Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya 60115, Indonesia
- Doctoral Program in Veterinary Science, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60115, Indonesia
| | - Mochammad Amin Alamsjah
- Department of Marine, Faculty of Fisheries and Marine, Universitas Airlangga, Surabaya 60115, Indonesia
| | - Muhamad Nur Ghoyatul Amin
- Department of Marine, Faculty of Fisheries and Marine, Universitas Airlangga, Surabaya 60115, Indonesia
| | | | - Pratiwi Pudjiastuti
- Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Surabaya 60115, Indonesia
| | - Khalijah Awang
- Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia
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Popescu-Vâlceanu HC, Stoicea MC, Enache V, Bratu RM, Mustăţea P, Drăguţ RM, Rusu E, Ionescu-Tîrgovişte C, Radulian G. Bcl-2 and p53 immunophenotypes in colorectal adenocarcinoma in type 2 diabetes mellitus versus non-diabetic patients. ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY = REVUE ROUMAINE DE MORPHOLOGIE ET EMBRYOLOGIE 2022; 63:521-528. [PMID: 36588490 PMCID: PMC9926153 DOI: 10.47162/rjme.63.3.06] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
We aimed to investigate immunohistochemical expression of the p53 tumor suppressor protein, and the B-cell lymphoma-2 (Bcl-2) apoptotic protein in colorectal adenocarcinoma patients with or without type 2 diabetes mellitus (T2DM). Tissue sections from 95 paraffin-embedded colorectal adenocarcinomas, originating from 52 T2DM and 43 non-diabetic patients, were immunostained for p53 [Ventana mouse monoclonal primary antibody (mAb) in vitro diagnostic (IVD) anti-p53, clone Bp53-11] and Bcl-2 (Ventana mAb IVD anti-Bcl-2, clone Bcl-2/124). Immunohistochemistry analysis did not find statistically significant differences between the two groups, but analysis on subgroups of patients in terms of presence or absence of obesity identified overexpression of p53 (>70% of cells) in the T2DM obese patients compared to non-diabetics. Overexpression of p53 was present in 80% of tumor cells coming from T2DM obese patients compared to 37.2% of tumor cells coming from non-diabetics obese and non-obese, and in 36.6% of tumor cells coming from non-diabetic non-obese patients (p=0.024). There was a single non-diabetic obese patient with p53 overexpression. Most cancer cells of T2DM obese patients presented more frequently p53 overexpression by comparison with cancer cells of the T2DM non-obese patients (80% vs 40.5%, p=0.028). Bcl-2/p53 co-expression was an infrequent event in T2DM patients' group. The results of this study suggest that patients with colorectal adenocarcinoma that associate T2DM and obesity exhibit higher p53 protein expression in malignant cells. In conclusion, our research highlights that obesity is a potential key factor in the relationship between T2DM and colorectal cancer.
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Affiliation(s)
| | - Mihai Ciprian Stoicea
- Department of Pathology, Regina Maria Central Reference Laboratory, Bucharest, Romania
| | - Valentin Enache
- Department of Pathology, Emergency Clinical Hospital, Bucharest, Romania
| | - Răzvan Matei Bratu
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Petronel Mustăţea
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Ramona Maria Drăguţ
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Emilia Rusu
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Constantin Ionescu-Tîrgovişte
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania , Department of Diabetes, Nutrition and Metabolic Diseases, Prof. Dr. N. C. Paulescu National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
| | - Gabriela Radulian
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania , Department of Diabetes, Nutrition and Metabolic Diseases, Prof. Dr. N. C. Paulescu National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
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24
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Li Q, Liu F, Tang Y, Lee S, Lang C, Bai L, Xia Y. The Distribution of Cardiovascular-Related Comorbidities in Different Adult-Onset Cancers and Related Risk Factors: Analysis of 10 Year Retrospective Data. Front Cardiovasc Med 2021; 8:695454. [PMID: 34595215 PMCID: PMC8476781 DOI: 10.3389/fcvm.2021.695454] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 08/19/2021] [Indexed: 12/25/2022] Open
Abstract
Introduction: Understanding the epidemiology of cardiovascular disease (CVD) related comorbidity is a key strategy for improving the outcomes of patients with cancer. Therefore, this study aimed to assess the distribution of cardiovascular comorbidities and cardiovascular risk factors (CVRF) among five cancer sites. Methods: This is a single-centered, cross-sectional study performed in Dalian, China. Between 2008 and 2018, all newly diagnosed cancer in the First Affiliated Hospital of Dalian Medical University, China were screened. Clinical data were extracted from a comprehensive electronic health record system. Results: 35861 patients with lung, colorectal, gastric, breast, and thyroid cancer were collected retrospectively. The most prevalent CVDs in descending order were hypertension (21.9%), followed by coronary heart disease (6.5%), atrial fibrillation (2.9%), and heart failure (1%). The prevalence of hypertension significantly varies between lung (21.3%), colorectal (27.3%), gastric (22.5%), breast (16.7%), and thyroid cancer (22.4%) (P < 0.001). CVRF varies with cancer sites. Age, sex, total cholesterol, triglyceride, low-density lipoprotein cholesterol, systolic blood pressure, smoking, alcohol use, and diabetes mellitus (DM) are common risk factors associated with CVD at different cancer sites. The association between DM and presence of CVD was strong in breast (odds ratio [OR] = 4.472, 95% confidence interval [CI]: 3.075-6.504, P < 0.001), lung (OR = 3.943; 95% CI: 3.270-4.754, P < 0.001), colorectal (OR = 3.049; 95% CI: 2.326-3.996, P < 0.001), and gastric (OR = 2.508; 95% CI: 1.927-3.264, P < 0.001) cancer. Conclusion: Cancer patients had a significant burden of CVD and increased CVRF. The prevalence of CVRF and CVD comorbidity differ for cancer types. DM remains significantly associated with CVD at different cancer sites except for thyroid cancer.
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Affiliation(s)
- Qingsong Li
- Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Fei Liu
- Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yuqi Tang
- Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Sharen Lee
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR China
| | - Chao Lang
- Yidu Cloud Technology, Ltd., Beijing, China
| | - Lan Bai
- Yidu Cloud Technology, Ltd., Beijing, China
| | - Yunlong Xia
- Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
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25
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Tonini V, Zanni M. Pancreatic cancer in 2021: What you need to know to win. World J Gastroenterol 2021; 27:5851-5889. [PMID: 34629806 PMCID: PMC8475010 DOI: 10.3748/wjg.v27.i35.5851] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 07/14/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is one of the solid tumors with the worst prognosis. Five-year survival rate is less than 10%. Surgical resection is the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage of the disease and surgery could be performed in a very limited number of patients. Moreover, surgery is still associated with high post-operative morbidity, while other therapies still offer very disappointing results. This article reviews every aspect of pancreatic cancer, focusing on the elements that can improve prognosis. It was written with the aim of describing everything you need to know in 2021 in order to face this difficult challenge.
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Affiliation(s)
- Valeria Tonini
- Department of Medical Sciences and Surgery, University of Bologna- Emergency Surgery Unit, IRCCS Sant’Orsola Hospital, Bologna 40121, Italy
| | - Manuel Zanni
- University of Bologna, Emergency Surgery Unit, IRCCS Sant'Orsola Hospital, Bologna 40121, Italy
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26
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Ranganath R, Chu Q. Global trends in pancreas cancer among Asia-Pacific population. J Gastrointest Oncol 2021; 12:S374-S386. [PMID: 34422401 DOI: 10.21037/jgo-20-118] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 08/26/2020] [Indexed: 12/12/2022] Open
Abstract
The incidence of pancreatic cancer is rising. Understanding trends of pancreatic cancer is crucial prior to putting policies and interventions in place. Countries with a high human development index (HDI) have a higher incidence, prevalence and mortality due to pancreatic cancer. This global trend is replicated in the Asia-Pacific countries with high HDI having higher incidence, prevalence and mortality due to pancreatic cancer. The incidence of pancreatic cancer is rising in the Asia-Pacific population as life expectancy increases with a rising HDI. Lack of good cancer registries has resulted in under reporting of pancreatic cancer in developing countries in the Asia-Pacific region. The mortality still remains high as in the Western world as most pancreatic cancers are diagnosed in an advanced stage of the disease due to non-availability of cost-effective screening tools with few patients receiving definitive care. Smoking, alcohol consumption, poor diet and obesity are significant modifiable risk factors contributing to the development of pancreatic cancer. Population based screening for pancreatic cancer is not cost-effective. Identification of hereditary and genetic factors in the Asia-Pacific population can help in targeted screening of high-risk individuals. Policies and interventions aimed at primary prevention have the greatest potential to be cost-effective yet impactful and reduce the disease burden.
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Affiliation(s)
- Rohit Ranganath
- Department of Surgery, Louisiana State University Health Sciences Center, Shreveport, LA, USA
| | - Quyen Chu
- Department of Surgery, Louisiana State University Health Sciences Center, Shreveport, LA, USA
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27
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Kumar S, Jach D, Macfarlane W, Crnogorac-Jurcevic T. A 3-Dimensional Coculture Model to Visualize and Monitor Interaction Between Pancreatic Cancer and Islet β Cells. Pancreas 2021; 50:982-989. [PMID: 34629448 DOI: 10.1097/mpa.0000000000001865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES To facilitate exploring a link between pancreatic ductal adenocarcinoma (PDAC) and diabetes mellitus, we constructed a novel 3-dimensional (3D) in vitro coculturing system for studying interactions between PDAC and islet cells. METHODS Adopting a 3D rotary cell culture system, we have cocultured several PDAC cell lines and MIN6 islet β cells. The cellular morphology and viability of both cell types were investigated by time-lapse imaging, confocal and scanning electron microscopy, and immunohistochemistry. RESULTS The developed coculture method enabled the formation of 3D PDAC and β-cell spheroids (pseudo islets). We showed that surface morphology and growth of cultured cells mimicked their in vivo appearance. In addition, the coculture demonstrated the affinity of the PDAC cells to grow around and invade the pseudo islets. CONCLUSIONS Using rotary cell culture system, we have established a simple in vitro 3D pancreatic model. It is a flexible culture system that can easily be expanded with the addition of various stromal/neural components to further mimic in vivo conditions, thus enabling holistic investigation of the endocrine and exocrine pancreas.
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MESH Headings
- Animals
- Carcinoma, Pancreatic Ductal/metabolism
- Carcinoma, Pancreatic Ductal/pathology
- Cell Communication
- Cell Culture Techniques, Three Dimensional/methods
- Cell Line, Tumor
- Cell Survival
- Coculture Techniques/methods
- Humans
- Immunohistochemistry
- Insulin-Secreting Cells/metabolism
- Insulin-Secreting Cells/pathology
- Mice
- Microscopy, Confocal
- Microscopy, Electron, Scanning
- Pancreatic Neoplasms/metabolism
- Pancreatic Neoplasms/pathology
- Spheroids, Cellular/metabolism
- Spheroids, Cellular/pathology
- Spheroids, Cellular/ultrastructure
- Time-Lapse Imaging/methods
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Affiliation(s)
- Sandeep Kumar
- From the Advance Therapy Unit, NHS Blood and Transplant, Barnsley
| | - Daria Jach
- Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London
| | - Wendy Macfarlane
- School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, United Kingdom
| | - Tatjana Crnogorac-Jurcevic
- Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London
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28
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Role of Annual Influenza Vaccination against Lung Cancer in Type 2 Diabetic Patients from a Population-Based Cohort Study. J Clin Med 2021; 10:jcm10153434. [PMID: 34362218 PMCID: PMC8347140 DOI: 10.3390/jcm10153434] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 07/14/2021] [Accepted: 07/16/2021] [Indexed: 01/16/2023] Open
Abstract
Type 2 diabetes mellitus (DM) patients are at a higher risk for developing lung cancer due to immune dysfunction and chronic inflammation. They also have increased morbidity and mortality related to influenza, and it is recommended that they receive an annual influenza vaccination. In this study, we evaluate whether influenza vaccination could reduce the incidence of lung cancer in DM patients. This cohort study included DM patients (≥55 years old) between 1 January 2002 and 31 December 2012 by using the Taiwan Health Insurance Database. Cox proportional hazard regression method was used to compare the relation between the influenza vaccination and lung cancer incidence after adjusting for potential confounders. Sub-group analyses were done according to vaccination status (unvaccinated, total number of vaccinations: 1, 2–3, ≥4) and evaluated the dose-dependent effects on lung cancer events. Among 22,252 eligible DM patients, 7860 (35.32%) received an influenza vaccination and 67.68% (14392) did not receive an influenza vaccination. Lung cancer incidence was significantly lower in the vaccinated group versus the unvaccinated group (adjusted HR 0.77; 95% CI 0.62–0.95, p < 0.05). Significant protective effects were observed among male sex (adjusted HR 0.72; 95% CI 0.55–0.94, p < 0.05) and 55–64 year (adjusted HR 0.61; 95% CI 0.40–0.94, p < 0.05) and ≥75 year (adjusted HR 0.63; 95% CI 0.42–0.92, p < 0.05) age groups, respectively. A dose-dependent protective effect was noted with a significant protective effect in those that received ≥4 vaccinations (adjusted HR 0.42; 95% CI 0.29–0.61, p < 0.001). In sub-group analysis, elder patients with ≥65 years of age were significantly protected from ≥4 vaccinations (adjusted HR 0.37; 95% CI 0.23–0.62, p < 0.001 in 65–74 years and adjusted HR 0.31; 95% CI 0.15–0.66, p = 0.002 in ≥75 years group, respectively). Male sex with ≥4 vaccinations had a significantly lower risk of lung cancer (adjusted HR 0.35; 95% CI 0.21–0.57, p < 0.001). Patients with comorbid conditions that received ≥4 vaccinations were also protected, and was especially significant among those with CCI ≥ 3 (adjusted HR 0.38; 95% CI 0.18–0.80, p = 0.009) as compared to 1 and 2–3 vaccination groups, including those with hypertension (adjusted HR 0.35; 95% CI 0.22–0.57, p < 0.001). This population-based cohort study demonstrated that annual influenza vaccination significantly reduced the lung cancer risk in DM patients and specifically demonstrates that a higher number of vaccinations is related with a more protective effect. Whether this is due to vaccine booster effects on anti-tumor immune regulation among DM patients still needs to be explored.
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29
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Guo S, Shi X, Gao S, Hou Q, Jiang L, Li B, Shen J, Wang H, Shen S, Zhang G, Pan Y, Liu W, Xu X, Zheng K, Shao Z, Jing W, Lin L, Li G, Jin G. The Landscape of Genetic Alterations Stratified Prognosis in Oriental Pancreatic Cancer Patients. Front Oncol 2021; 11:717989. [PMID: 34368001 PMCID: PMC8340855 DOI: 10.3389/fonc.2021.717989] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 07/08/2021] [Indexed: 11/13/2022] Open
Abstract
Background Pancreatic cancer is a life-threatening malignant disease with significant diversity among geographic regions and races leading to distinct carcinogenesis and prognosis. Previous studies mainly focused on Western patients, while the genomic landscape of Oriental patients, especially Chinese, remained less investigated. Methods A total of 408 pancreatic cancer patients were enrolled. A panel containing 436 cancer-related genes was used to detect genetic alterations in tumor samples. Results We profiled the genomic alteration landscape of pancreatic duct adenocarcinoma (PDAC), intraductal papillary mucinous neoplasm (IPMN), periampullary carcinoma (PVC), and solid-pseudopapillary tumor (SPT). Comparison with a public database revealed specific gene mutations in Oriental PDAC patients including higher mutation rates of DNA damage repair-related genes. Analysis of mutational signatures showed potential heterogenous carcinogenic factors caused by diabetes mellitus. KRAS mutation, especially KRAS G12D mutation, was associated with poor survival, while patients not harboring the 17 significant copy number variations (CNVs) had a better prognosis. We further identified multiple correlations between clinicopathologic variables and genetic mutations, as well as CNVs. Finally, by network-based stratification, three classes of PDAC patients were robustly clustered. Among these, class 1 (characterized by the Fanconi anemia pathway) achieved the best outcome, while class 2 (involved in the platinum drug resistance pathway) suffered from the worst prognosis. Conclusions In this study, we reported for the first time the genetic alteration landscape of Oriental PDAC patients identifying many Oriental-specific alterations. The relationship between genetic alterations and clinicopathological factors as well as prognosis demonstrated important genomic impact on tumor biology. This study will help to optimize clinical treatment of Oriental PDAC patients and improve their survival.
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Affiliation(s)
- Shiwei Guo
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Xiaohan Shi
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China.,Department of General Surgery, Naval Medical Center of People's Liberation Army (PLA), Shanghai, China
| | - Suizhi Gao
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Qunxing Hou
- Zhangjiang Center for Translational Medicine, Shanghai Biotecan Medical Diagnostics Co., Ltd, Shanghai, China
| | - Lisha Jiang
- Zhangjiang Center for Translational Medicine, Shanghai Biotecan Medical Diagnostics Co., Ltd, Shanghai, China
| | - Bo Li
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Jing Shen
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Huan Wang
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Shuo Shen
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - GuoXiao Zhang
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Yaqi Pan
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Wuchao Liu
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Xiongfei Xu
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Kailian Zheng
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Zhuo Shao
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Wei Jing
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Ling Lin
- Zhangjiang Center for Translational Medicine, Shanghai Biotecan Medical Diagnostics Co., Ltd, Shanghai, China
| | - Gang Li
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Gang Jin
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
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Zhang Y, Zhang T, Yang W, Chen H, Geng X, Li G, Chen H, Wang Y, Li L, Sun B. Beneficial Diets and Pancreatic Cancer: Molecular Mechanisms and Clinical Practice. Front Oncol 2021; 11:630972. [PMID: 34123787 PMCID: PMC8193730 DOI: 10.3389/fonc.2021.630972] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 04/19/2021] [Indexed: 01/02/2023] Open
Abstract
Pancreatic cancer (PC) is a malignant tumor with high invasiveness, easy metastatic ability, and chemoresistance. Patients with PC have an extremely low survival rate due to the difficulty in early diagnosis. It is estimated that nearly 90% of PC cases are caused by environmental risk factors. Approximately 50% of PC cases are induced by an unhealthy diet, which can be avoided. Given this large attribution to diet, numerous studies have assessed the relationship between various dietary factors and PC. This article reviews three beneficial diets: a ketogenic diet (KD), a Mediterranean diet (MD), and a low-sugar diet. Their composition and impact mechanism are summarized and discussed. The associations between these three diets and PC were analyzed, and we aimed to provide more help and new insights for the prevention and treatment of PC.
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Affiliation(s)
- Yang Zhang
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Tao Zhang
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Wenbo Yang
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hongze Chen
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xinglong Geng
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Guanqun Li
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hua Chen
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yongwei Wang
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Le Li
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.,Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, China
| | - Bei Sun
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.,Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, China
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31
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Monroy-Iglesias MJ, Dolly S, Sarker D, Thillai K, Van Hemelrijck M, Santaolalla A. Pancreatic Cancer Exposome Profile to Aid Early Detection and Inform Prevention Strategies. J Clin Med 2021; 10:1665. [PMID: 33924591 PMCID: PMC8069449 DOI: 10.3390/jcm10081665] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/19/2021] [Accepted: 04/08/2021] [Indexed: 12/12/2022] Open
Abstract
Pancreatic cancer (PCa) is associated with a poor prognosis and high mortality rate. The causes of PCa are not fully elucidated yet, although certain exposome factors have been identified. The exposome is defined as the sum of all environmental factors influencing the occurrence of a disease during a life span. The development of an exposome approach for PCa has the potential to discover new disease-associated factors to better understand the carcinogenesis of PCa and help with early detection strategies. Our systematic review of the literature identified several exposome factors that have been associated with PCa alone and in combination with other exposures. A potential inflammatory signature has been observed among the interaction of several exposures (i.e., smoking, alcohol consumption, diabetes mellitus, obesity, and inflammatory markers) that further increases the incidence and progression of PCa. A large number of exposures have been identified such as genetic, hormonal, microorganism infections and immune responses that warrant further investigation. Future early detection strategies should utilize this information to assess individuals' risk for PCa.
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Affiliation(s)
- Maria J. Monroy-Iglesias
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK; (M.J.M.-I.); (M.V.H.)
| | - Saoirse Dolly
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK; (S.D.); (D.S.); (K.T.)
| | - Debashis Sarker
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK; (S.D.); (D.S.); (K.T.)
- School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK
| | - Kiruthikah Thillai
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK; (S.D.); (D.S.); (K.T.)
| | - Mieke Van Hemelrijck
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK; (M.J.M.-I.); (M.V.H.)
| | - Aida Santaolalla
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK; (M.J.M.-I.); (M.V.H.)
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Jin Q, Hart PA, Shi N, Joseph JJ, Donneyong M, Conwell DL, Clinton SK, Cruz-Monserrate Z, Brasky TM, Tinker LF, Liu S, Shadyab AH, Thomson CA, Qi L, Rohan T, Tabung FK. Dietary Patterns of Insulinemia, Inflammation and Glycemia, and Pancreatic Cancer Risk: Findings from the Women's Health Initiative. Cancer Epidemiol Biomarkers Prev 2021; 30:1229-1240. [PMID: 33827986 DOI: 10.1158/1055-9965.epi-20-1478] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 12/11/2020] [Accepted: 03/29/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Pancreatic cancer risk is increasing in countries with high consumption of Western dietary patterns and rising obesity rates. We examined the hypothesis that specific dietary patterns reflecting hyperinsulinemia (empirical dietary index for hyperinsulinemia; EDIH), systemic inflammation (empirical dietary inflammatory pattern; EDIP), and postprandial glycemia [glycemic index (GI); glycemic load (GL)] are associated with pancreatic cancer risk, including the potential modifying role of type 2 diabetes (T2D) and body mass index (BMI). METHODS We calculated dietary scores from baseline (1993-1998) food frequency questionnaires among 129,241 women, 50-79 years-old in the Women's Health Initiative. We used multivariable-adjusted Cox regression to estimate HRs and 95% confidence intervals (95% CI) for pancreatic cancer risk. RESULTS During a median 19.9 years of follow-up, 850 pancreatic cancer cases were diagnosed. We observed no association between dietary scores and pancreatic cancer risk overall. However, risk was elevated among participants with longstanding T2D (present >3 years before pancreatic cancer diagnosis) for EDIH. For each 1 SD increment in dietary score, the HRs (95% CIs) were: EDIH, 1.33 (1.06-1.66); EDIP, 1.26 (0.98-1.63); GI, 1.26 (0.96-1.67); and GL, 1.23 (0.96-1.57); although interactions were not significant (all P interaction >0.05). Separately, we observed inverse associations between GI [0.86 (0.76-0.96), P interaction = 0.0068] and GL [0.83 (0.73-0.93), P interaction = 0.0075], with pancreatic cancer risk among normal-weight women. CONCLUSIONS We observed no overall association between the dietary patterns evaluated and pancreatic cancer risk, although women with T2D appeared to have greater cancer risk. IMPACT The elevated risk for hyperinsulinemic diets among women with longstanding T2D and the inverse association among normal-weight women warrant further examination.
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Affiliation(s)
- Qi Jin
- Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, Ohio
| | - Phil A Hart
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Ni Shi
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, Ohio
| | - Joshua J Joseph
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | | | - Darwin L Conwell
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Steven K Clinton
- Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, Ohio.,The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, Ohio.,Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Zobeida Cruz-Monserrate
- Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, Ohio.,Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.,The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, Ohio
| | - Theodore M Brasky
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, Ohio.,Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.,Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, Ohio
| | - Lesley F Tinker
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Simin Liu
- Department of Epidemiology, Brown University, Providence, Rhode Island
| | - Aladdin H Shadyab
- Department of Family Medicine and Public Health, School of Medicine, University of California San Diego, La Jolla, California
| | - Cynthia A Thomson
- Department of Health Promotion Sciences, Mel & Enid Zuckerman College of Public Health, The University of Arizona, Tucson, Arizona
| | - Lihong Qi
- School of Medicine, University of California Davis, Davis, California
| | - Thomas Rohan
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
| | - Fred K Tabung
- Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, Ohio. .,The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, Ohio.,Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.,Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, Ohio
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Lu H, Han X, Ren J, Ren K, Li Z, Zhang Q. Metformin attenuates synergic effect of diabetes mellitus and Helicobacter pylori infection on gastric cancer cells proliferation by suppressing PTEN expression. J Cell Mol Med 2021; 25:4534-4542. [PMID: 33760349 PMCID: PMC8107109 DOI: 10.1111/jcmm.15967] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 09/20/2020] [Accepted: 09/22/2020] [Indexed: 12/17/2022] Open
Abstract
It has been reported that CagA of Helicobacter pylori reduced PTEN expression by enhancing its promoter methylation. Furthermore, diabetes mellitus (DM) may also promote the methylation status of PTEN, a tumour suppressor gene in gastric cancer (GC). It is intriguing to explore whether DM may strengthen the tumorigenic effect of H pylori (HP) by promoting the methylation of PTEN promoter and whether the administration of metformin may reduce the risk of GC by suppressing the methylation of PTEN promoter. In this study, we enrolled 107 GC patients and grouped them as HP(-)DM(-) group, HP(+)DM(-) group and HP(+)DM(+) group. Bisulphite sequencing PCR evaluated methylation of PTEN promoter. Quantitative real-time PCR, immunohistochemistry and Western blot, immunofluorescence, flow cytometry and MTT assay were performed accordingly. DNA methylation of PTEN promoter was synergistically enhanced in HP(+)DM(+) patients, and the expression of PTEN was suppressed in HP(+)DM(+) patients. Cell apoptosis was decreased in HP(+)DM(+) group. Metformin showed an apparent effect on restoring CagA-induced elevation of PTEN promoter methylation, thus attenuating the PTEN expression. The reduced PTEN level led to increased proliferation and inhibited apoptosis of HGC-27 cells. In this study, we collected GC tumour tissues from GC patients with or without DM/HP to compare their PTEN methylation and expression while testing the effect of metformin on the methylation of PTEN promoter. In summary, our study suggested that DM could strengthen the tumorigenic effect of HP by promoting the PTEN promoter methylation, while metformin reduces GC risk by suppressing PTEN promoter methylation.
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Affiliation(s)
- Huibin Lu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jianzhuang Ren
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Kewei Ren
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zongming Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Quanhui Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Zhang M, Hu X, Kang Y, Xu W, Yang X. Association between fasting blood glucose levels at admission and overall survival of patients with pancreatic cancer. BMC Cancer 2021; 21:131. [PMID: 33549043 PMCID: PMC7866692 DOI: 10.1186/s12885-021-07859-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 01/31/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The associations between fasting blood glucose and staging and overall survival of patients with pancreatic cancer are still controversial. This study aimed to investigate the association between fasting blood glucose levels and overall survival (OS) of patients with pancreatic cancer and to evaluate the impact of differentiation and staging of pancreatic cancer. METHODS This was a retrospective study of patients with pathologically confirmed pancreatic cancer admitted to Shengjing Hospital of China Medical University between 01/2012 and 12/2016. The outcome was the OS. The factors associated with OS were examined using univariable and multivariable Cox and logistic regression analyses. RESULTS A total of 253 patients were included. Preoperative blood glucose levels were not significantly associated with the OS of patients with pancreatic cancer (HR = 1.04, 95%CI: 0.78-1.40, P = 0.781). Only CA199 > 1000 was independently associated with OS (HR = 1.86, 95%CI: 1.15-3.02, P = 0.012). The median survival in the normal glucose group was 20.5 months (95% confidence interval (CI): 14.2-26.9). The median survival in the high glucose group was 14.2 months (95% CI: 9.7-18.6). There was no statistically significant difference between the two groups (P = 0.573). Multivariable logistic regression analyses were performed to determine if blood glucose levels influenced the 1- and 2-year OS. No significant association was observed for 1-year (OR = 1.27, 95%CI: 0.71-2.29, P = 0.418) or 2-year (HR = 1.37, 95%CI: 0.76-2.46, P = 0.296) OS. CONCLUSIONS Fasting blood glucose levels are not associated with the OS of patients with pancreatic adenocarcinoma.
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Affiliation(s)
- Mingming Zhang
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiaoru Hu
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ye Kang
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wanfeng Xu
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xianghong Yang
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China.
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Menini S, Iacobini C, Vitale M, Pesce C, Pugliese G. Diabetes and Pancreatic Cancer-A Dangerous Liaison Relying on Carbonyl Stress. Cancers (Basel) 2021; 13:313. [PMID: 33467038 PMCID: PMC7830544 DOI: 10.3390/cancers13020313] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/09/2021] [Accepted: 01/14/2021] [Indexed: 02/06/2023] Open
Abstract
Both type 2 (T2DM) and type 1 (T1DM) diabetes mellitus confer an increased risk of pancreatic cancer in humans. The magnitude and temporal trajectory of the risk conferred by the two forms of diabetes are similar, suggesting a common mechanism. Carbonyl stress is a hallmark of hyperglycemia and dyslipidemia, which accompanies T2DM, prediabetes, and obesity. Accumulating evidence demonstrates that diabetes promotes pancreatic ductal adenocarcinoma (PDAC) in experimental models of T2DM, a finding recently confirmed in a T1DM model. The carbonyl stress markers advanced glycation end-products (AGEs), the levels of which are increased in diabetes, were shown to markedly accelerate tumor development in a mouse model of Kras-driven PDAC. Consistently, inhibition of AGE formation by trapping their carbonyl precursors (i.e., reactive carbonyl species, RCS) prevented the PDAC-promoting effect of diabetes. Considering the growing attention on carbonyl stress in the onset and progression of several cancers, including breast, lung and colorectal cancer, this review discusses the mechanisms by which glucose and lipid imbalances induce a status of carbonyl stress, the oncogenic pathways activated by AGEs and their precursors RCS, and the potential use of carbonyl-scavenging agents and AGE inhibitors in PDAC prevention and treatment, particularly in high-risk diabetic individuals.
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Affiliation(s)
- Stefano Menini
- Department of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, Italy; (S.M.); (C.I.); (M.V.)
| | - Carla Iacobini
- Department of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, Italy; (S.M.); (C.I.); (M.V.)
| | - Martina Vitale
- Department of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, Italy; (S.M.); (C.I.); (M.V.)
| | - Carlo Pesce
- Department of Neurosciences, Rehabilitation, Ophtalmology, Genetic and Maternal Infantile Sciences (DINOGMI), Department of Excellence of MIUR, University of Genoa Medical School, 16132 Genoa, Italy;
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, Italy; (S.M.); (C.I.); (M.V.)
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Wang L, Zhong L, Xu B, Chen M, Huang H. Diabetes mellitus and the risk of ovarian cancer: a systematic review and meta-analysis of cohort and case-control studies. BMJ Open 2020; 10:e040137. [PMID: 33376163 PMCID: PMC7778773 DOI: 10.1136/bmjopen-2020-040137] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 10/05/2020] [Accepted: 11/18/2020] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE Emerging evidence from observational studies (cohort and case-control studies) suggests that a history of diabetes mellitus (DM) has been linked to increased risk of ovarian cancer (OC), but the association between them remains inconclusive. The aim of this systematic review and meta-analysis of observational studies was to clarify this association. DESIGN Systematic review and meta-analysis. METHODS We searched PubMed, Embase and the Cochrane library databases published from the inception through 9 April 2020 without language restriction. Observational studies that evaluated the correlation between DM and the incidence of OC were included in our study. Relative risk (RR) with 95% CI was pooled by use of a random-effects model. RESULTS A total of 36 epidemiological articles, including 9 case-control and 27 cohort studies, were finally enrolled, consisting of 14 496 incident cases of OC. Synthesised RRs of developing OC by history of DM were 1.20 (95% CI=1.10 to 1.31) for all eligible studies, 1.08 (95% CI=0.77 to 1.53) for case-control studies and 1.22 (95% CI=1.11 to 1.33) for cohort studies. The above-mentioned positive association persisted across most of subgroup analyses, whereas it was not significant among studies from North American and European countries, level of unadjusted, and patients with low-quality and gestational DM group. The cumulative meta-analysis and sensitivity analysis showed pooled effect was stable and reliable, and no apparent publication bias was identified in this study. CONCLUSIONS Our study found weaker but still association between DM and OC risk. However, further well-designed prospective studies that control for potential confounders are warranted.
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Affiliation(s)
- Lihai Wang
- Obstetrics and Gynecology, Huzhou Central Hospital, Affiliated Central Hospital, HuZhou University, Huzhou, Zhejiang, China
| | - Lei Zhong
- Intensive Care Unit, Huzhou Central Hospital, Affiliated Central Hospital, HuZhou University, Huzhou, Zhejiang, China
| | - Bin Xu
- Obstetrics and Gynecology, Huzhou Central Hospital, Affiliated Central Hospital, HuZhou University, Huzhou, Zhejiang, China
| | - Min Chen
- Obstetrics and Gynecology, Huzhou Central Hospital, Affiliated Central Hospital, HuZhou University, Huzhou, Zhejiang, China
| | - Hongxiao Huang
- Obstetrics and Gynecology, Huzhou Central Hospital, Affiliated Central Hospital, HuZhou University, Huzhou, Zhejiang, China
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Jentzsch V, Davis JAA, Djamgoz MBA. Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management. Cancers (Basel) 2020; 12:E3096. [PMID: 33114159 PMCID: PMC7690843 DOI: 10.3390/cancers12113096] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 10/09/2020] [Indexed: 02/07/2023] Open
Abstract
The most common form of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which comprises some 85% of all cases. Currently, this is the fourth highest cause of cancer mortality worldwide and its incidence is rising steeply. Commonly applied clinical therapies offer limited chance of a lasting cure and the five-year survival rate is one of the lowest of the commonly occurring cancers. This review cultivates the hypothesis that the best management of PDAC would be possible by integrating 'western' clinical medicine with evidence-based complementary measures. Protecting the liver, where PDAC frequently first spreads, is also given some consideration. Overall, the complementary measures are divided into three groups: dietary factors, nutraceutical agents and lifestyle. In turn, dietary factors are considered as general conditioners, multi-factorial foodstuffs and specific compounds. The general conditioners are alkalinity, low-glycemic index and low-cholesterol. The multi-factorial foodstuffs comprise red meat, fish, fruit/vegetables, dairy, honey and coffee. The available evidence for the beneficial effects of the specific dietary and nutraceutical agents was considered at four levels (in order of prominence): clinical trials, meta-analyses, in vivo tests and in vitro studies. Thus, 9 specific agents were identified (6 dietary and 3 nutraceutical) as acceptable for integration with gemcitabine chemotherapy, the first-line treatment for pancreatic cancer. The specific dietary agents were the following: Vitamins A, C, D and E, genistein and curcumin. As nutraceutical compounds, propolis, triptolide and cannabidiol were accepted. The 9 complementary agents were sub-grouped into two with reference to the main 'hallmarks of cancer'. Lifestyle factors covered obesity, diabetes, smoking, alcohol and exercise. An integrative treatment regimen was devised for the management of PDAC patients. This involved combining first-line gemcitabine chemotherapy with the two sub-groups of complementary agents alternately in weekly cycles. The review concludes that integrated management currently offers the best patient outcome. Opportunities to be investigated in the future include emerging modalities, precision medicine, the nerve input to tumors and, importantly, clinical trials.
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Affiliation(s)
- Valerie Jentzsch
- Department of Life Sciences, Neuroscience Solutions to Cancer Research Group, Imperial College London, South Kensington Campus, London SW7 2AZ, UK; (V.J.); (J.A.A.D.)
- Business School, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
| | - James A. A. Davis
- Department of Life Sciences, Neuroscience Solutions to Cancer Research Group, Imperial College London, South Kensington Campus, London SW7 2AZ, UK; (V.J.); (J.A.A.D.)
| | - Mustafa B. A. Djamgoz
- Department of Life Sciences, Neuroscience Solutions to Cancer Research Group, Imperial College London, South Kensington Campus, London SW7 2AZ, UK; (V.J.); (J.A.A.D.)
- Biotechnology Research Centre, Cyprus International University, Haspolat, Nicosia, TRNC, Mersin 10, Turkey
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Yi ZH, Luther Y, Xiong GH, Ni YL, Yun F, Chen J, Yang Z, Zhang Q, Kuang YM, Zhu YC. Association between diabetes mellitus and lung cancer: Meta-analysis. Eur J Clin Invest 2020; 50:e13332. [PMID: 32589285 DOI: 10.1111/eci.13332] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 06/04/2020] [Accepted: 06/16/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND This study aimed to summarize the association between diabetes mellitus (DM) and the incidence of lung cancer using a meta-analysis of cohort studies. MATERIALS AND METHODS We systematically searched PubMed, Embase and the Cochrane Library to identify potential cohort studies. Relative risk (RR) was used to calculate the association between DM and the risk of lung cancer. Subgroup analysis, sensitivity analysis and test for publication bias were performed. Twenty cohort studies were selected. RESULTS The participants with DM showed little or no significant effect on the risk of lung cancer (RR: 1.10; 95% CI: 0.99-1.23; P = .087). DM was not associated with the risk of lung cancer in men (RR: 1.11; 95%CI: 0.92-1.35; P = .270), but a significant association was observed in women (RR: 1.18; 95%CI: 1.10-1.28; P < .001). Subgroup analysis suggested that smoker status was confounding variables that could bias the relationship between DM and the incidence of lung cancer. CONCLUSIONS This meta-analysis suggests that DM has no significant impact on the incidence of lung cancer in men but has a harmful effect on women.
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Affiliation(s)
- Zi-Han Yi
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, China
| | - Yannick Luther
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, China
| | - Guo-Hang Xiong
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, China
| | - Yue-Li Ni
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, China
| | - Fang Yun
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, China
| | - Jing Chen
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, China
| | - Zhe Yang
- Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
| | - Qiao Zhang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, China
| | - Ying-Min Kuang
- Department of Organ Transplantation, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Yue-Chun Zhu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, China
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Tseng CM, Wang HH, Wang WL, Lee CT, Tai CM, Tseng CH, Chen CC, Tsai YN, Sun MS, Hsu YC. Prognostic Impact of Diabetes Mellitus on Overall Survival in a Nationwide Population-Based Cohort of Patients With Pancreatic Cancer. Endocr Pract 2020; 26:707-713. [PMID: 33471638 DOI: 10.4158/ep-2019-0565] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 01/29/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Diabetes mellitus (DM) is a risk factor for pancreatic cancer but its prognostic impact remains controversial. We aimed to investigate the association between long-standing DM and the risk of mortality. METHODS This population-based cohort study analyzed data from the national healthcare database in Taiwan. We identified all patients diagnosed with pancreatic cancer and excluded those who were diagnosed with DM with-in 2 years of the cancer diagnosis. Eligible patients were grouped into long-standing DM (>2 years) and nondiabetic controls, and were compared for overall survival using a Cox proportional hazard model. Sensitivity tests stratified by cancer stages (as indicated by specific treatment) were performed. RESULTS Patients with long-standing DM were significantly older (mean age, 71.38 years versus 66.0 years; P<.0001) and had a higher Charlson comorbidity index (9.53 versus 6.78; P<.0001) and diabetes comorbidity severity index (2.38 versus 0.82; P<.0001) compared with the non-DM controls. Although the unadjusted analysis showed a higher risk of mortality in the patients with long-term DM (crude hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.20 to 1.33; P<.0001), the association became insignificant after adjustment for age, sex, and comorbidity index (adjusted HR, 1.01; 95% CI, 0.95 to 1.06, P = .84). Subgroup analyses also showed no association between long-term DM and mortality in various subgroups stratified by cancer treatment. CONCLUSION After adjusting for associated comorbidities and complications, long-standing DM per se was not an independent prognostic factor for overall survival in this nationwide population-based cohort with pancreatic cancer. ABBREVIATIONS CCI = Charlson Comorbidity Index; CI = confidence interval; DCSI = Diabetes Complication Severity Index; DM = diabetes mellitus; HR = hazard ratio; ICD = International Classification of Diseases; NHIRD = National Health Insurance Research Database; RCIPD = Registry for Catastrophic Illness Patient Database.
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Affiliation(s)
- Chao-Ming Tseng
- Division of Gastroenterology and Hepatology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Hsi-Hao Wang
- Division of Nephrology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; School of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Wen-Lun Wang
- Division of Gastroenterology and Hepatology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Ching-Tai Lee
- Division of Gastroenterology and Hepatology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Chi-Ming Tai
- Division of Gastroenterology and Hepatology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Cheng-Hao Tseng
- Division of Gastroenterology and Hepatology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Chih-Cheng Chen
- Division of Gastroenterology and Hepatology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Ying-Nan Tsai
- Division of Gastroenterology and Hepatology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Meng-Shun Sun
- Division of Gastroenterology, Yuan's General Hospital, Kaohsiung, Taiwan
| | - Yao-Chun Hsu
- Division of Gastroenterology and Hepatology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; School of Medicine, I-Shou University, Kaohsiung, Taiwan; Center for Liver Diseases, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan..
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Sato K, Hikita H, Myojin Y, Fukumoto K, Murai K, Sakane S, Tamura T, Yamai T, Nozaki Y, Yoshioka T, Kodama T, Shigekawa M, Sakamori R, Tatsumi T, Takehara T. Hyperglycemia enhances pancreatic cancer progression accompanied by elevations in phosphorylated STAT3 and MYC levels. PLoS One 2020; 15:e0235573. [PMID: 32609742 PMCID: PMC7329089 DOI: 10.1371/journal.pone.0235573] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 06/18/2020] [Indexed: 01/20/2023] Open
Abstract
Diabetes mellitus is a well-known risk factor for pancreatic cancer. We focused on hyperglycemia, a main feature of diabetes mellitus, and uncovered its effect on precancerous pancreatic intraepithelial neoplasia (PanIN) progression. In vivo induction of hyperglycemia with 100 mg/kg streptozotocin in KrasLSL G12DPdx1Cre (KP) mice promoted the PanIN formation and progression. Preconditioning with a high- or low-glucose medium for 28 days showed that a high-glucose environment increased cell viability and sphere formation in PANC-1, a Kras-mutant human pancreatic ductal adenocarcinoma cell line, and mPKC1, a Kras-mutant murine pancreatic cancer cell line. In contrast, no changes were observed in BxPC3, a Kras-wild-type human pancreatic cancer cell line. Orthotopic injection of mPKC1 into the pancreatic tails of BL6/J mice showed that cells maintained in high-glucose medium grew into larger tumors than did those maintained in low-glucose medium. Hyperglycemia strengthened the STAT3 phosphorylation, which was accompanied by elevated MYC expression in Kras-mutant cells. Immunohistochemistry showed stronger phosphorylated STAT3 (pSTAT3) and MYC staining in PanINs from diabetic KP mice than in those from euglycemic counterparts. STAT3 inhibition with 1 μM STAT3 inhibitor STATTIC in Kras-mutant pancreatic cell lines blocked the cell viability- and sphere formation-enhancing effects of the hyperglycemic environment and reversed the elevated pSTAT3 and MYC expression. MYC knockdown did not affect cell viability but did reduce sphere formation. No decrease in pSTAT3 expression was observed upon siMYC treatment. In conclusion, hyperglycemia, on a Kras-mutant background, aggravates the PanIN progression, which is accompanied by elevated pSTAT3 and MYC expression.
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Affiliation(s)
- Katsuhiko Sato
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yuta Myojin
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kenji Fukumoto
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kazuhiro Murai
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Sadatsugu Sakane
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Takeshi Tamura
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Takuo Yamai
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yasutoshi Nozaki
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Teppei Yoshioka
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Takahiro Kodama
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Minoru Shigekawa
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Tomohide Tatsumi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
- * E-mail:
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Abstract
Debate is ongoing regarding the relationship between type 2 diabetes and cancer, and the pathways linking the two are incompletely understood. Some posit that the relationship hinges on a common predisposing factor such as obesity, insulin resistance, or chronic inflammation that increases the risk of cancer independently. Others speculate that diabetes acts as an independent risk factor for cancer because of other molecular pathways and interactions. Additionally, antidiabetic medications have been associated with changes in cancer risk. This review presents a summary of the latest studies and data concerning the relationships among type 2 diabetes, antidiabetic medications, cancer risk, and cancer prognosis.
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Kaleru T, Vankeshwaram VK, Maheshwary A, Mohite D, Khan S. Diabetes Mellitus in the Middle-Aged and Elderly Population (>45 Years) and Its Association With Pancreatic Cancer: An Updated Review. Cureus 2020; 12:e8884. [PMID: 32742851 PMCID: PMC7388804 DOI: 10.7759/cureus.8884] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Diabetes mellitus (DM) and pancreatic cancer (PC) in the elderly are widely considered to be interrelated. New-onset diabetes (NOD) patients are considered a high-risk group for the development of PC within three years of diagnosis. We reviewed the literature to determine the pathophysiological association between DM and PC, which can help in the development of screening tests for early PC diagnosis in the elderly with NOD. We also studied the potential associations between them after pancreaticoduodenectomy (PD) or pancreatic resection. We collected studies published in the last five years in PubMed that are relevant to DM and PC in the elderly. We mainly focused on the pathophysiology and intracellular mechanisms involved between NOD and PC. We illustrated the clinical signs and immunological and metabolic biomarkers that can be used to diagnose early PC in the elderly with NOD. In the 34 studies we reviewed, five showed that long-term diabetes mellitus (LTDM) increases the risk of PC. Six studies showed that NOD in the elderly is an early sign of PC. Fourteen studies proposed that clinical signs and biomarker levels should be used to determine the high-risk risk group for PC among NOD patients. Six studies reported that NOD is associated with the worst outcomes postoperatively, and three studies showed that patients developed DM after pancreatic resection. LTDM is considered an independent risk factor for PC development in the elderly. NOD is a consequence and maybe the only early presenting sign of PC. Screening protocols and tests should be used in clinical practice to determine the proportion of NOD patients who should undergo further testing for early diagnosis of PC. DM and PC are also co-related postoperatively and patients should be monitored for impaired glucose levels, overall survival, and mortality.
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Affiliation(s)
- Thanmai Kaleru
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | | | - Ankush Maheshwary
- Neurology, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
- Medicine, Government Medical College, Amritsar, IND
| | - Divya Mohite
- Neurology, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
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Wang M, Yang Y, Liao Z. Diabetes and cancer: Epidemiological and biological links. World J Diabetes 2020; 11:227-238. [PMID: 32547697 PMCID: PMC7284016 DOI: 10.4239/wjd.v11.i6.227] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 04/24/2020] [Accepted: 05/05/2020] [Indexed: 02/06/2023] Open
Abstract
The incidence of diabetes and cancer has increased significantly in recent years. Furthermore, there are many common risk factors for both diabetes and cancer, such as obesity, sedentary lifestyle, smoking, and ageing. A large body of epidemiological evidence has indicated that diabetes is considered as an independent risk factor for increased rates of heterogeneous types of cancer occurrence and death. The incidence and mortality of various types of cancer, such as pancreas, liver, colorectal, breast, endometrial, and bladder cancers, have a modest growth in diabetics. However, diabetes may work as a protective factor for prostate cancer. Although the underlying biological mechanisms have not been totally understood, studies have validated that insulin/insulin-like growth factor (IGF) axis (including insulin resistance, hyperinsulinemia, and IGF), hyperglycemia, inflammatory cytokines, and sex hormones provide good circumstances for cancer cell proliferation and metastasis. Insulin/IGF axis activates several metabolic and mitogenic signaling pathways; hyperglycemia provides energy for cancer cell growth; inflammatory cytokines influence cancer cell apoptosis. Thus, these three factors affect all types of cancer, while sex hormones only play important roles in breast cancer, endometrial cancer, and prostate cancer. This minireview consolidates and discusses the epidemiological and biological links between diabetes and various types of cancer.
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Affiliation(s)
- Mina Wang
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
- The Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing 100010, China
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yingying Yang
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna 17177, Sweden
- Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Zehuan Liao
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
- Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Solna 17177, Sweden
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Linkeviciute-Ulinskiene D, Patasius A, Zabuliene L, Stukas R, Smailyte G. Increased Risk of Site-Specific Cancer in People with Type 2 Diabetes: A National Cohort Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 17:ijerph17010246. [PMID: 31905811 PMCID: PMC6982113 DOI: 10.3390/ijerph17010246] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Revised: 12/26/2019] [Accepted: 12/28/2019] [Indexed: 12/11/2022]
Abstract
A retrospective cohort design was used with the objective to evaluate cancer risk among people with type 2 diabetes mellitus (T2DM) in Lithuania. The cohort was established by identifying all patients with the first diagnosis of T2DM in the National Health Insurance Fund database during 2000-2012. Cancer cases were identified by record linkage with the Lithuanian Cancer Registry. Standardized incidence ratios (SIRs) were calculated. Of the 127,290 people that were included, 5959 cases of cancer in men and 6661 cancer cases in women with T2DM were observed. A statistically significant increase in risk for all cancer sites was observed in women, SIR 1.16 (95% CI 1.14-1.19), but not in men, SIR 1.00 (95% CI 0.98-1.03). Among males, a significant increase of liver (SIR 2.11, 95% CI 1.79-2.49]), pancreas (SIR 1.77, 95% CI 1.57-1.99), kidney (SIR 1.46 95% CI 1.31-1.62), thyroid (SIR 1.83, 95% CI 1.32-2.54), colorectal (SIR 1.23, 95% CI 1.14-1.31]), skin melanoma (SIR 1.40, 95% CI 1.11-1.76), and non-melanoma skin (SIR 1.14, 95% CI 1.05-1.23) cancer was observed. For females with T2DM, a significant increase in risk of cancer of the liver (SIR 1.45, 95% CI 1.17-1.79), pancreas (SIR 1.74, 95% CI 1.56-1.93), kidney (SIR = 1.43, 95% CI 1.28-1.60), thyroid (SIR = 1.40, 95% CI 1.22-1.62), breast (SIR = 1.24, 95% CI 1.17-1.31), and corpus uteri (SIR 2.07, 95% CI 1.93-2.21) was observed. In conclusion, people with T2DM in Lithuania had an increased risk of site-specific cancer.
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Affiliation(s)
- Donata Linkeviciute-Ulinskiene
- Institute of Biomedical Sciences, Department of Pathology, Forensic Medicine and Pharmacology, Faculty of Medicine, Vilnius University, Ciurlionio g. 21, 03101 Vilnius, Lithuania
- Correspondence: ; Tel.: +46-73-665-5998
| | - Ausvydas Patasius
- Laboratory of Cancer Epidemiology, National Cancer Institute, P. Baublio g. 3b, 08406 Vilnius, Lithuania; (A.P.); (G.S.)
- Institute of Health Sciences, Faculty of Medicine, Vilnius University, Ciurlionio g. 21, 03101 Vilnius, Lithuania;
| | - Lina Zabuliene
- Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Santariskiu g. 2, 08406 Vilnius, Lithuania;
| | - Rimantas Stukas
- Institute of Health Sciences, Faculty of Medicine, Vilnius University, Ciurlionio g. 21, 03101 Vilnius, Lithuania;
| | - Giedre Smailyte
- Laboratory of Cancer Epidemiology, National Cancer Institute, P. Baublio g. 3b, 08406 Vilnius, Lithuania; (A.P.); (G.S.)
- Institute of Health Sciences, Faculty of Medicine, Vilnius University, Ciurlionio g. 21, 03101 Vilnius, Lithuania;
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Loghmani L, Saedi N, Omani-Samani R, Safiri S, Sepidarkish M, Maroufizadeh S, Esmailzadeh A, Shokrpour M, Khedmati Morasae E, Almasi-Hashiani A. Tubal ligation and endometrial Cancer risk: a global systematic review and meta-analysis. BMC Cancer 2019; 19:942. [PMID: 31604465 PMCID: PMC6788032 DOI: 10.1186/s12885-019-6174-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 09/20/2019] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Studies on relationship between tubal ligation and endometrial cancer have led to contradictory findings. In several studies, however, a reduced endometrial cancer risk was suggested following tubal ligation. Therefore, a systematic review and meta-analysis was conducted to examine the relationship between tubal ligation and endometrial cancer risk. METHODS In this systematic review and meta-analysis, PubMed/Medline, Web of Science, Scopus, Embase, and Google Scholar were searched for relevant studies published up to May 30th, 2018. We compared endometrial cancer risk in women with and without tubal ligation in retrieved studies. RESULTS Two hundred nine studies were initially retrieved from the data bases. After exclusion of duplicates and studies which did not meet inclusion criteria, ten cohort and case-control studies, including 6,773,066 cases, were entered into the quantitative meta-analysis. There was 0.90% agreement between two researchers who searched and retrieved the studies. The summary OR (SOR) was reported using a random effect model. Begg's test suggested that there was no publication bias, but a considerable heterogeneity was observed (I2 = 95.4%, P = 0.001). We pooled the raw number of tables cells (i.e. a, b, c, and d) of eight studies. The SOR suggested that tubal ligation was significantly associated with a lower risk of endometrial cancer (SOR = 0.577, 95% CI = 0.420-0.792). Also, given the rare nature of endometrial cancer (< 5%), different effect sizes were considered as comparable measures of risk. Therefore we pooled ten studies and SOR of these studies revealed that tubal ligation was significantly associated with a lower risk of endometrial cancer (SOR = 0.696, 95% CI = 0.425-0.966). Besides that, we pooled eight studies in which adjusted effect sizes were reported and a subsequent analysis revealed that the summary estimate of adjusted odds ratio (SAOR) was significant (SAOR = 0.862, 95% CI = 0.698-1.026). CONCLUSIONS This study revealed a protective effect of tubal ligation on endometrial cancer risk (approximately 42% lower risk of cancer). It is recommended that studies should be designed to reveal mechanisms of this relationship.
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Affiliation(s)
- Laleh Loghmani
- Department of Nursing, Faculty of Nursing and Midwifery, Bam University of Medical Sciences, Bam, Iran
| | - Nafise Saedi
- Department of Gynecologic Oncology, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Omani-Samani
- Department of Medical Ethics and Law, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Saeid Safiri
- Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Community Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahdi Sepidarkish
- Department of Biostatistics and Epidemiology, Babol University of Medical Sciences, Babol, Iran
| | - Saman Maroufizadeh
- School of Nursing and Midwifery, Guilan University of Medical Sciences, Rasht, Iran
| | - Arezoo Esmailzadeh
- Department of Obstetrics and Gynecology, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Maryam Shokrpour
- Department of Obstetrics and Gynecology, Arak University of Medical Sciences, Arak, Iran
| | - Esmaeil Khedmati Morasae
- Institute of Psychology, Health, and Society, Department of Health Services Research, University of Liverpool, Liverpool, UK
| | - Amir Almasi-Hashiani
- Department of Epidemiology, School of Health, Arak University of Medical Sciences, Arak, Iran. .,Traditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, Iran.
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Naudin S, Viallon V, Hashim D, Freisling H, Jenab M, Weiderpass E, Perrier F, McKenzie F, Bueno-de-Mesquita HB, Olsen A, Tjønneland A, Dahm CC, Overvad K, Mancini FR, Rebours V, Boutron-Ruault MC, Katzke V, Kaaks R, Bergmann M, Boeing H, Peppa E, Karakatsani A, Trichopoulou A, Pala V, Masala G, Panico S, Tumino R, Sacerdote C, May AM, van Gils CH, Rylander C, Borch KB, Chirlaque López MD, Sánchez MJ, Ardanaz E, Quirós JR, Amiano Exezarreta P, Sund M, Drake I, Regnér S, Travis RC, Wareham N, Aune D, Riboli E, Gunter MJ, Duell EJ, Brennan P, Ferrari P. Healthy lifestyle and the risk of pancreatic cancer in the EPIC study. Eur J Epidemiol 2019; 35:975-986. [PMID: 31564045 DOI: 10.1007/s10654-019-00559-6] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 09/03/2019] [Indexed: 12/27/2022]
Abstract
= 4.9e-04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.
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Affiliation(s)
- Sabine Naudin
- Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer, World Health Organization, 150, Cours Albert Thomas, 69372, Lyon Cedex 08, France
| | - Vivian Viallon
- Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer, World Health Organization, 150, Cours Albert Thomas, 69372, Lyon Cedex 08, France
| | - Dana Hashim
- Department of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Heinz Freisling
- Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer, World Health Organization, 150, Cours Albert Thomas, 69372, Lyon Cedex 08, France
| | - Mazda Jenab
- Nutritional Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Elisabete Weiderpass
- Director Office, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Flavie Perrier
- Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer, World Health Organization, 150, Cours Albert Thomas, 69372, Lyon Cedex 08, France
| | - Fiona McKenzie
- Environment and Radiation section, Agency for Research on Cancer, World Health Organization, Lyon, France
| | - H Bas Bueno-de-Mesquita
- Departement for Determinants of Chronic Diseases (Former), National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.,Department of Gastroenterology and Hepathology, University Medical Center, Utrecht, The Netherlands.,Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Anja Olsen
- Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Anne Tjønneland
- Danish Cancer Society Research Center, Copenhagen, Denmark.,Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Christina C Dahm
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Kim Overvad
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.,Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
| | - Francesca R Mancini
- CESP, Faculté de médecine (USVQ), Université Paris-Sud, INSERM, Université Paris-Saclay, Villejuif, France.,Inserm UMR1018, Institut Gustave Roussy, Villejuif, France
| | - Vinciane Rebours
- Pancreatology Department, Beaujon Hospital, AP-HP, Clichy, France.,Inserm UMR1149, DHU Unit, Paris-Diderot University, Paris, France
| | - Marie-Christine Boutron-Ruault
- CESP, Faculté de médecine (USVQ), Université Paris-Sud, INSERM, Université Paris-Saclay, Villejuif, France.,Inserm UMR1018, Institut Gustave Roussy, Villejuif, France
| | - Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Manuela Bergmann
- German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany
| | - Heiner Boeing
- German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany
| | | | - Anna Karakatsani
- Hellenic Health Foundation, Athens, Greece.,Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, ATTIKON University Hospital of Athens, Haidari, Greece
| | - Antonia Trichopoulou
- Hellenic Health Foundation, Athens, Greece.,School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Valeria Pala
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Giovana Masala
- Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy
| | - Salvatore Panico
- Department of Clinical and Experimental Medecine, University Federico II, Naples, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Department, Civic M.P.Arezzo Hospital, Ragusa, Italy
| | - Carlotta Sacerdote
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University, Hospital and Center for Cancer Prevention (CPO), Turin, Italy
| | - Anne M May
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Carla H van Gils
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Charlotta Rylander
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - Kristin Benjaminsen Borch
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - María Dolores Chirlaque López
- Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain.,Spanish Consortium for Research and Public Health (CIBERESP), Madrid, Spain
| | - Maria-Jose Sánchez
- Spanish Consortium for Research and Public Health (CIBERESP), Madrid, Spain.,Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria, Universidad de Granada, Granada, Spain
| | - Eva Ardanaz
- Spanish Consortium for Research and Public Health (CIBERESP), Madrid, Spain.,Navarra Public Health Institute, Pamplona, Spain.,IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | | | - Pilar Amiano Exezarreta
- Spanish Consortium for Research and Public Health (CIBERESP), Madrid, Spain.,Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain
| | - Malin Sund
- Department of Surgical and Preoperative Sciences, Umeå University, Umeå, Sweden
| | - Isabel Drake
- Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden
| | - Sara Regnér
- Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden
| | - Ruth C Travis
- Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
| | - Nick Wareham
- MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
| | - Dagfinn Aune
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.,Department of Nutrition, Bjørknes University College, Oslo, Norway.,Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Marc J Gunter
- Nutritional Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Eric J Duell
- Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
| | - Paul Brennan
- Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Pietro Ferrari
- Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer, World Health Organization, 150, Cours Albert Thomas, 69372, Lyon Cedex 08, France.
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Pizzato M, Turati F, Rosato V, La Vecchia C. Exploring the link between diabetes and pancreatic cancer. Expert Rev Anticancer Ther 2019; 19:681-687. [PMID: 31287962 DOI: 10.1080/14737140.2019.1642109] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Epidemiological studies indicate an association between type 2 diabetes and pancreatic cancer but the complex and multidirectional relationship between them remains unclear. Areas covered: We summarized epidemiological evidence on diabetes and pancreatic cancer exploring the time-risk relationship. We described mechanisms linking long-standing diabetes to pancreatic cancer. We discussed pancreatic cancer-associated diabetes and its implication in the early detection of pancreatic cancer. Expert opinion: The markedly increased risk of pancreatic cancer in patients with new-onset diabetes compared with long-standing diabetes observed in several epidemiological studies indicates a complex and bidirectional connection, with long-standing diabetes being a predisposing factor for pancreatic cancer (increasing the risk of the malignancy 1.5- to 2-fold) and new-onset diabetes an early manifestation of the tumor. Identifying clinical features and biomarkers to distinguish pancreatic cancer-associated diabetes from type 2 diabetes is an important goal to improve management and survival of this cancer. Imaging (MRI) for middle-age patients with new-onset diabetes may be considered.
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Affiliation(s)
- Margherita Pizzato
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano , Milan , Italy
| | - Federica Turati
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano , Milan , Italy
| | - Valentina Rosato
- Unit of Medical Statistics and Biometry, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano , Milano , Italy
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano , Milan , Italy
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48
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Maisonneuve P. Epidemiology and burden of pancreatic cancer. Presse Med 2019; 48:e113-e123. [PMID: 30878335 DOI: 10.1016/j.lpm.2019.02.030] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 02/13/2019] [Indexed: 02/07/2023] Open
Abstract
Pancreatic cancer, although infrequent, has a very poor prognosis, making it currently the fourth common causes of cancer mortality in most developed countries including the European Union (EU). Its incidence varies across regions, which suggests that lifestyle factors play an important role in its etiology, although part of the variation could be ascribed to difference in diagnostic and coding practices. Because pancreatic cancer is strongly age-dependent, increasing population longevity and ageing will lead to an increase of the global burden of pancreatic cancer. It was estimated that, by 2040, the total number of cases in the EU will increase by more than 30%. Pancreatic cancer is a multifactorial disease and many risk factors have been identified. Hereditary factors are responsible for less than 10% of the cases while tobacco smoking and excess body weight, the two most important potentially modifiable risk factors, are responsible for 10 to 30% of the cases, affording a unique opportunity for preventing one of our deadliest cancers.
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Affiliation(s)
- Patrick Maisonneuve
- Unit of Clinical Epidemiology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
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49
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Wang G, Yin L, Peng Y, Gao Y, Gao H, Zhang J, Lv N, Miao Y, Lu Z. Insulin promotes invasion and migration of KRAS G12D mutant HPNE cells by upregulating MMP-2 gelatinolytic activity via ERK- and PI3K-dependent signalling. Cell Prolif 2019; 52:e12575. [PMID: 30838710 PMCID: PMC6536446 DOI: 10.1111/cpr.12575] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Revised: 12/16/2018] [Accepted: 12/18/2018] [Indexed: 12/11/2022] Open
Abstract
Objectives Hyperinsulinemia is a risk factor for pancreatic cancer, but the function of insulin in carcinogenesis is unclear, so this study aimed to elucidate the carcinogenic effects of insulin and the synergistic effect with the KRAS mutation in the early stage of pancreatic cancer. Materials and methods A pair of immortalized human pancreatic duct‐derived cells, hTERT‐HPNE E6/E7/st (HPNE) and its oncogenic KRASG12D variant, hTERT‐HPNE E6/E7/KRASG12D/st (HPNE‐mut‐KRAS), were used to investigate the effect of insulin. Cell proliferation, migration and invasion were assessed using Cell Counting Kit‐8 and transwell assays, respectively. The expression of E‐cadherin, N‐cadherin, vimentin and matrix metalloproteinases (MMP‐2, MMP‐7 and MMP‐9) was evaluated by Western blotting and/or qRT‐PCR. The gelatinase activity of MMP‐2 and MMP‐9 in conditioned media was detected using gelatin zymography. The phosphorylation status of AKT, GSK3β, p38, JNK and ERK1/2 MAPK was determined by Western blotting. Results The migration and invasion ability of HPNE cells was increased after the introduction of the mutated KRAS gene, together with an increased expression of MMP‐2. These effects were further enhanced by the simultaneous administration of insulin. The use of MMP‐2 siRNA confirmed that MMP‐2 was involved in the regulation of cell invasion. Furthermore, there was a concentration‐ and time‐dependent increase in gelatinase activity after insulin treatment, which could be reversed by an insulin receptor tyrosine kinase inhibitor (HNMPA‐(AM)3). In addition, insulin markedly enhanced the phosphorylation of PI3K/AKT, p38, JNK and ERK1/2 MAPK pathways, with wortmannin or LY294002 (a PI3K‐specific inhibitor) and PD98059 (a MEK1‐specific inhibitor) significantly inhibiting the insulin‐induced increase in MMP‐2 gelatinolytic activity. Conclusions Taken together, these results suggest that insulin induced migration and invasion in HPNE and HPNE‐mut‐KRAS through PI3K/AKT and ERK1/2 activation, with MMP‐2 gelatinolytic activity playing a vital role in this process. These findings may provide a new therapeutic target for preventing carcinogenesis and the evolution of pancreatic cancer with a background of hyperinsulinemia.
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Affiliation(s)
- Guangfu Wang
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Lingdi Yin
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Yunpeng Peng
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Yong Gao
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Hao Gao
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Jingjing Zhang
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Nan Lv
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Yi Miao
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Zipeng Lu
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Pancreas Institute, Nanjing Medical University, Nanjing, China
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50
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Setiawan VW, Stram DO, Porcel J, Chari ST, Maskarinec G, Le Marchand L, Wilkens LR, Haiman CA, Pandol SJ, Monroe KR. Pancreatic Cancer Following Incident Diabetes in African Americans and Latinos: The Multiethnic Cohort. J Natl Cancer Inst 2019; 111:27-33. [PMID: 29917105 PMCID: PMC6335114 DOI: 10.1093/jnci/djy090] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 03/08/2018] [Accepted: 04/17/2018] [Indexed: 12/18/2022] Open
Abstract
Background Diabetes has been proposed to be a risk factor for and a consequence of pancreatic cancer (PC). The relationship between recent-onset diabetes and PC is not well understood, and data in minorities are sparse. We examined the relationships between recent-onset diabetes and PC incidence in African Americans and Latinos in the Multiethnic Cohort. Methods A total of 48 995 African Americans and Latinos without prior diabetes and cancer at baseline (1993-1996) were included in the study. Questionnaires, Medicare data, and California hospital discharge files were used to identify new diabetes diagnoses. Cox regressions were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer associated with diabetes and with diabetes duration. Results A total of 15 833 (32.3%) participants developed diabetes between baseline and 2013. A total of 408 incident PC cases were identified during follow-up. Diabetes was associated with PC (HRage75 = 2.39, 95% CI = 1.91 to 2.98). Individuals with recent-onset diabetes (within three or fewer years of PC diagnosis) had a greater risk compared with those with long-term diabetes across all ages. The HRage75 for recent-onset diabetes was 4.08 (95% CI = 2.76 to 6.03) in Latinos and 3.38 (95% CI = 2.30 to 4.98) in African Americans. Conclusions Diabetes was associated with a more than twofold higher risk of PC in African Americans and Latinos, but recent-onset diabetes was associated with a 2.3-fold greater increase in risk of PC than long-standing diabetes. Our findings support the hypothesis that recent-onset diabetes is a manifestation of PC and that long-standing diabetes is a risk factor for this malignancy.
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Affiliation(s)
- Veronica Wendy Setiawan
- Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA
- Norris Comprehensive Cancer Center, Keck School of Medicine of University of Southern California, Los Angeles, CA
| | - Daniel O Stram
- Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA
| | - Jacqueline Porcel
- Norris Comprehensive Cancer Center, Keck School of Medicine of University of Southern California, Los Angeles, CA
| | - Suresh T Chari
- Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN
| | | | - Loïc Le Marchand
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI
| | - Lynne R Wilkens
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI
| | - Christopher A Haiman
- Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA
- Norris Comprehensive Cancer Center, Keck School of Medicine of University of Southern California, Los Angeles, CA
| | - Stephen J Pandol
- Division of Gastroenterology, Departments of Medicine, Cedars-Sinai Medical Center and Department of Veterans Affairs, Los Angeles, CA
| | - Kristine R Monroe
- Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA
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