Leukocyte telomere length and its interaction with germline variation in telomere-related genes in relation to pancreatic adenocarcinoma risk
Menée aux Etats-Unis à l'aide de données de registres et auprès de 1 460 patients atteints d'un adénocarcinome canalaire du pancréas et 1 459 témoins (âge moyen : 65 ans ; 56% d'hommes), cette étude analyse l'association entre la longueur des télomères leucocytaires périphériques et le risque de développer la maladie, puis examine l'effet, sur cette association, de polymorphismes à simple nucléotide connus pour faire varier la longueur des télomères
Résumé en anglais
Background: Leukocyte telomere length (LTL) has been associated with risk of multiple cancers, but its association with pancreatic ductal adenocarcinoma (PDAC) is unclear. We investigated the association between peripheral blood LTL and PDAC risk, and examined effect modification by candidate single-nucleotide polymorphisms (SNPs) previously reported to be associated with variation in LTL.
Methods: A case-control study of 1460 PDAC cases and 1459 frequency-matched controls was performed using biospecimens and data from the Mayo Clinic Biospecimens Resource for Pancreas Research. Quantitative PCR was used to measure LTL and then categorized into tertiles based on sex-specific control distribution. Eleven telomere-related SNPs were also genotyped. Logistic regression was used to calculate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs).
Results: Shorter peripheral blood LTL was associated with a higher risk of PDAC (ORT1vsT3=1.26, 95%CI=1.03-1.54, Ptrend=0.02, ORcontinuous=1.14, 95%CI=1.02-1.28), but the association was restricted to cases with treatment-naïve blood samples (OR T1vsT3=1.51, 95%CI=1.16-1.96, Ptrend=0.002; ORcontinuous=1.25, 95%CI=1.08-1.45) and not cases whose blood samples were collected after initiation of cancer therapy (OR T1vsT3=1.10, 95%CI=0.87-1.39, Ptrend=0.42; ORcontinuous=1.08, 95%CI=0.94-1.23). Three SNPs (TERC-rs10936599, ACYP2-rs11125529, and TERC-rs1317082) were each associated with inter-individual variation in LTL among controls, but there was no evidence of effect modification by these SNPs.
Conclusions: Treatment-naïve short LTL is associated with higher risk of PDAC, and the association does not differ by germline variation in the candidate telomere-related SNPs examined. Impact: Peripheral blood LTL might serve as a molecular marker for risk modeling to identify persons at high-risk of PDAC.
