title: Leucocyte telomere length, genetic variants at theTERTgene region and risk of pancreatic cancer.
abstract: 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 theTERTregion 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 atTERT(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 theTERTgene region were associated with risk of pancreatic cancer.
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
authors: Ying
authors: Y
authors: Bao
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
authors: Jennifer
authors: J
authors: Prescott
authors: 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.
authors: Chen
authors: C
authors: Yuan
authors: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Mingfeng
authors: M
authors: Zhang
authors: 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.
authors: Peter
authors: P
authors: Kraft
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors: Ana
authors: A
authors: Babic
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors: Vicente
authors: V
authors: Morales-Oyarvide
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors: Zhi Rong
authors: ZR
authors: Qian
authors: 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.
authors: Julie E
authors: JE
authors: Buring
authors: University of Washington School of Nursing, Seattle, Washington, USA.
authors: Barbara B
authors: BB
authors: Cochrane
authors: 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.
authors: J Michael
authors: JM
authors: Gaziano
authors: 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.
authors: Edward L
authors: EL
authors: Giovannucci
authors: 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.
authors: JoAnn E
authors: JE
authors: Manson
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors: Kimmie
authors: K
authors: Ng
authors: 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.
authors: Shuji
authors: S
authors: Ogino
authors: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
authors: Thomas E
authors: TE
authors: Rohan
authors: 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.
authors: Howard D
authors: HD
authors: Sesso
authors: 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.
authors: Meir J
authors: MJ
authors: Stampfer
authors: 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.
authors: Charles S
authors: CS
authors: Fuchs
authors: 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.
authors: Immaculata
authors: I
authors: De Vivo
authors: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Laufey T
authors: LT
authors: Amundadottir
authors: 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.
authors: Brian M
authors: BM
authors: Wolpin
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology* / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007962:Leukocytes; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*; D059506:Telomere Shortening; D014481:United States / Q000453:epidemiology
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: PANCREATIC CANCER