Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer
Year: 2016
Type: article
Study design: Observational Study
Abstract: Objective 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. Design 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. Results 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; p trend =0.048). Results remained unchanged after adjustment for diabetes, body mass index and physical activity. Three SNPs at TERT (linkage disequilibrium r 2 <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). Conclusions Prediagnostic leucocyte telomere length and genetic variants at the TERT gene region were associated with risk of pancreatic cancer.
Source: Gut
Authors: Ying Bao, Jennifer Prescott, Chen Yuan, Mingfeng Zhang, Peter Kraft, Ana Babic, Vicente Morales-Oyarvide, Zhi Rong Qian, Julie E Buring, Barbara B Cochrane, J Michael Gaziano, Edward L Giovannucci, JoAnn E Manson, Kimmie Ng, Shuji Ogino, Thomas E Rohan, Howard D Sesso, Meir J Stampfer, Charles S Fuchs, Immaculata De Vivo, Laufey T Amundadottir, Brian M Wolpin
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1044130170, Women's Health Initiative, Dana Farber/ Harvard Cancer Center SPORE in Gastrointestinal Cancer, G1214533002, G1318872084, Women's Health Initiative, G1416987869, G1423636853, G1485268950, G151562090, Women's Health Initiative, G1652679434, Prospective Cohort Collaborative in Pancreatic Cancer Epidemiology & Pathogenesis, Women's Health Initiative, G2214254730, G229684361, G2417273319, G2449723990, G2505739775, G257474614, Biochemical Markers in the nurses' Health Study Cohort, G2652994630, G2750880407, G2789075706, G2852769941, G3101773556, G3219722387, Women's Health Initiative Memory Study (WHIMS), G3416405943, G3426488059, G3544793024, G3544898838, Women's Health Initiative, G361298724, G370776200, G3754462075, G3901341770, Dietary and Hormonal Determinants of Cancer in Women, Women's Health Initiative, Women's Health Initiative, G4065499244, G419469450, COORDINATING CENTER FOR WOMEN'S HEALTH INITIATIVE, G4368349855, G4376790518, G4454202622, G4522543292, G4560602636, G4582778782, G459566519, G4715825192, G4750830274, G484043965, G4940723635, G50637022, G5143030701, FOR ALL FIELD CENTER FOR WHI EXTENSION, Physicians' Health Study II: Prevention Trial of Vitamins, G5448612825, G5457525012, G5520316217, G558986044, G5748837154, G5932435930, G5953211031, TRIAL OF ASPIRIN AND BETA-CAROTENE IN U S MD'S, Women's Health Initiative, G6781161026, TRIAL OF ASPIRIN AND VITAMIN E IN WOMEN, Women's Health Initiative, G709447011, Women's Health Initiative, Harvard Clinical and Translational Science Center, G7554740352, G7582705761, Women's Health Study: Continued Follow-up, Cancer Epidemiology Cohort in Male Health Professionals, G814381192, G8152339232, G8288886904, G8554986239, G8780700017, G885693336, G9000007102, G9000019617, G9000043482, G9000050131, G9000058182, G9000069684, G9000070405, G9000072420, G9000099730, G9000106048, G9000122174, G9000157792, G9000190097, G9000207199, G9000217803, G9000230008, G9000240940, G9000282402, G9000285876, G9000291457, G9000330701, G9000343153, Altered metabolism and machine learning for pancreatic cancer early detection, Yale Clinical and Translational Science Award, G939971039, G994665467, G999174792
OpenAlex ID: W2533406433