Leukocyte Telomere Length in Relation to Pancreatic Cancer Risk: A Prospective Study

Abstract

Background: Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originally motivating many of these studies was that shorter telomeres would be associated with an increase in cancer risk; the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. Two studies have addressed the association of LTL in relation to pancreatic cancer risk and the results are contrasting.Methods: We measured LTL in a prospective study of 331 pancreatic cancer cases and 331 controls in the context of the European Prospective Investigation into Cancer and Nutrition (EPIC).Results: We observed that the mean LTL was higher in cases (0.59 AE 0.20) than in controls (0.57 AE 0.17), although this difference was not statistically significant (P ¼ 0.07), and a basic logistic regression model showed no association of LTL with pancreas cancer risk. When adjusting for levels of HbA1c and C-peptide, however, there was a weakly positive association between longer LTL and pancreatic cancer risk [OR, 1.13; 95% confidence interval (CI), 1.01-1.27]. Additional analyses by cubic spline regression suggested a possible nonlinear relationship between LTL and pancreatic cancer risk (P ¼ 0.022), with a statistically nonsignificant increase in risk at very low LTL, as well as a significant increase at high LTL.Conclusion: Taken together, the results from our study do not support LTL as a uniform and strong predictor of pancreatic cancer.Impact: The results of this article can provide insights into telomere dynamics and highlight the complex relationship between LTL and pancreatic cancer risk. Cancer Epidemiol Biomarkers Prev; 23(11); 2447-54. Ó2014 AACR.

TERT gene harbors multiple variants associated with pancreatic cancer susceptibility

“…46 It is interesting to note that in two recent prospective studies, longer LTL have been shown to be associated with increased risk of pancreatic cancer. 47,48 This is consistent with our finding that the G allele, which is associated with decreased pancreatic cancer risk in our study, is also associated with shorter telomeres in the study by Melin et al 46 Thus, it is possible that the link between rs2853677 and pancreatic cancer occurs via the variation of telomere length and, in particular, that the A allele leads to constitutively longer telomeres, which may, in turn, be responsible for the increase in pancreatic cancer risk. On the other hand, in another study, based on a retrospective case-control study, shorter telomeres were associated with increased risk of pancreatic cancer.…”

Association of peripheral leukocyte telomere length and its variation with pancreatic cancer and colorectal cancer risk in Chinese population

“…van Heek et al also reported that telomere shortening was nearly universal in pancreatic intraepithelial neoplasia [39]. In this context, only three studies, including one case-control study which found short telomeres and extremely long telomeres in peripheral blood are associated with an increased risk for pancreatic cancer [12], and two nested case-control studies which presented the inconsistent results [28, 29]. However, none of the studies was conducted in Asians, not to say Chinese.…”

“…LTL has become a biomarker of biological ageing and risk of age-related diseases, like cancers, cardiovascular disease and diabetes [26, 27]. So far, only three studies have investigated circulating LTL and risk of pancreatic cancer [12, 28, 29], while none of them were conducted in Asians. Additionally, recent studies also showed that telomere length variation (TLV) across all chromosomal ends, which could increase chromosome instability and poor clinical outcome, contributed to the risk of bladder cancer [30].…”

Telomere Length and Pancreatic Cancer Risk—Reply

“…13 A study of the European Prospective Investigation into Cancer and Nutrition (EPIC) found no significant association between leukocyte telomere length and pancreatic cancer; however, in a secondary analysis using cubic spline regression, the investigators found evidence for a non-linear relationship. 14 …”