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1468-3288 66 6 2017 06 Gut Gut Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer. 1116-1122 10.1136/gutjnl-2016-312510 Telomere shortening occurs as an early event in pancreatic tumorigenesis, and genetic variants at the telomerase reverse transcriptase (TERT) gene region have been associated with pancreatic cancer risk. However, it is unknown whether prediagnostic leucocyte telomere length is associated with subsequent risk of pancreatic cancer. We measured prediagnostic leucocyte telomere length in 386 pancreatic cancer cases and 896 matched controls from five prospective US cohorts. ORs and 95% CIs were calculated using conditional logistic regression. Matching factors included year of birth, cohort (which also matches on sex), smoking status, fasting status and month/year of blood collection. We additionally examined single-nucleotide polymorphisms (SNPs) at the TERT region in relation to pancreatic cancer risk and leucocyte telomere length using logistic and linear regression, respectively. Shorter prediagnostic leucocyte telomere length was associated with higher risk of pancreatic cancer (comparing extreme quintiles of telomere length, OR 1.72; 95% CI 1.07 to 2.78; ptrend=0.048). Results remained unchanged after adjustment for diabetes, body mass index and physical activity. Three SNPs at TERT (linkage disequilibrium r2<0.25) were associated with pancreatic cancer risk, including rs401681 (per minor allele OR 1.33; 95% CI 1.12 to 1.59; p=0.002), rs2736100 (per minor allele OR 1.36; 95% CI 1.13 to 1.63; p=0.001) and rs2736098 (per minor allele OR 0.75; 95% CI 0.63 to 0.90; p=0.002). The minor allele for rs401681 was associated with shorter telomere length (p=0.023). Prediagnostic leucocyte telomere length and genetic variants at the TERT gene region were associated with risk of pancreatic cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/. Bao Ying Y Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. Prescott Jennifer J Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. Yuan Chen C Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Zhang Mingfeng M Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Kraft Peter P Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. Babic Ana A Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Morales-Oyarvide Vicente V Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Qian Zhi Rong ZR Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Buring Julie E JE Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, Massachusetts, USA. Cochrane Barbara B BB University of Washington School of Nursing, Seattle, Washington, USA. Gaziano J Michael JM Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System. Giovannucci Edward L EL Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. Manson JoAnn E JE Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Ng Kimmie K Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Ogino Shuji S Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Rohan Thomas E TE Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA. Sesso Howard D HD Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Stampfer Meir J MJ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. Fuchs Charles S CS Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. De Vivo Immaculata I Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. Amundadottir Laufey T LT Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Wolpin Brian M BM Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. eng KL2 TR001100 TR NCATS NIH HHS United States N01WH42129 WH WHI NIH HHS United States N01WH32111 WH WHI NIH HHS United States N01WH32100 WH WHI NIH HHS United States R35 CA197735 CA NCI NIH HHS United States N01WH32122 WH WHI NIH HHS United States N01WH44221 WH WHI NIH HHS United States U01 CA210171 CA NCI NIH HHS United States N01WH24152 WH WHI NIH HHS United States P01 CA087969 CA NCI NIH HHS United States UL1 TR001863 TR NCATS NIH HHS United States R01 HL043851 HL NHLBI NIH HHS United States R01 HL034595 HL NHLBI NIH HHS United States N01WH32118 WH WHI NIH HHS United States R01 CA124908 CA NCI NIH HHS United States N01WH32115 WH WHI NIH HHS United States R01 CA034944-03 CA NCI NIH HHS United States UM1 CA186107 CA NCI NIH HHS United States R01 HL026490 HL NHLBI NIH HHS United States R01 CA047988 CA NCI NIH HHS United States N01WH42107 WH WHI NIH HHS United States N01WH32105 WH WHI NIH HHS United States R01 HL080467 HL NHLBI NIH HHS United States UM1 CA167552 CA NCI NIH HHS United States K07 CA140790 CA NCI NIH HHS United States R01 HL034595-07 HL NHLBI NIH HHS United States R01 CA049449 CA NCI NIH HHS United States R01 CA040360 CA NCI NIH HHS United States R01 HL026490-03 HL NHLBI NIH HHS United States P50 CA127003 CA NCI NIH HHS United States N01WH32119 WH WHI NIH HHS United States R01 CA097193 CA NCI NIH HHS United States N01WH32108 WH WHI NIH HHS United States R01 CA034944 CA NCI NIH HHS United States N01WH22110 WH WHI NIH HHS United States Journal Article Observational Study Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't 2016 10 21
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