Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer

Gut. 2017 Jun;66(6):1116-1122. doi: 10.1136/gutjnl-2016-312510. Epub 2016 Oct 21.


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; 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).

Conclusions: Prediagnostic leucocyte telomere length and genetic variants at the TERT gene region were associated with risk of pancreatic cancer.


Publication types

  • 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

MeSH terms

  • Adenocarcinoma / epidemiology*
  • Adenocarcinoma / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Leukocytes
  • Male
  • Middle Aged
  • Odds Ratio
  • Pancreatic Neoplasms / epidemiology*
  • Pancreatic Neoplasms / genetics*
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Telomerase / genetics*
  • Telomere Shortening*
  • United States / epidemiology


  • TERT protein, human
  • Telomerase

Grant support