Long telomeres raise pancreatic cancer risk
Longer telomeres increase the overall risk of pancreatic cancer, according to a recent Singapore study.
“These findings, together with results from prior studies, support a potential aetiological role of longer telomeres for the development of pancreatic cancer,” said researchers.
Drawing from the Singapore Chinese Health Study, researchers identified 26,540 participants whose telomere lengths were measured using monochrome multiplex quantitative polymerase chain reaction. Cells subjected to telomere measurements were from peripheral blood samples. Incident pancreatic cancer and related deaths were assessed by linking the study cohort to the Singapore Cancer Registry, as well as to the Birth and Death Registry.
Over a mean follow-up of 13 years, 116 participants (mean age, 66.24±7.86; 51.72 percent male) developed pancreatic cancer. Those who were free of the malignancy tended to be younger and female (n=26,422; mean age, 62.80±7.64; 46.07 percent male). [PLoS One 2019;14:e0221697]
Researchers grouped the participants according to telomere length, revealing a significant and direct correlation with the risk of pancreatic cancer. Patients belonging to the highest category were more than twice as likely to be diagnosed with the malignancy relative to their lowest-quartile counterparts (hazard ratio [HR], 2.18, 95 percent CI, 1.25–3.80; p-trend=0.02).
This effect was driven by incident cases of adenocarcinoma. Patients in the top vs bottom quartiles of telomere length were significantly more likely to develop the malignancy (HR, 2.50, 1.22–5.13; p-trend=0.02).
Even when taken as a continuous variable, telomere length remained significantly correlated with the risks of overall pancreatic cancer (HR, 2.29, 1.07–4.92) and adenocarcinoma (HR, 3.08, 1.17–8.11).
In contrast, telomere length did not seem to influence the risk of pancreatic cancers of nonadenocarcinoma or unknown histologies (continuous: HR, 1.47, 0.43–5.06; Q4 vs Q1: HR, 1.63, 0.66–4.03; p-trend=0.23).
Subsequent subgroup analyses were performed to account for potential demographic heterogeneities. Telomere length remained significantly correlated with pancreatic risk in never smokers (HR, 3.04 1.43–6.47; p-trend=0.007), but not in ever smokers; in males (HR, 2.91, 1.32–6.41; p-trend=0.03), but not in females.
Similarly, telomere length was predictive of malignancy risk only in those without a history of diabetes (HR, 2.50, 1.33–4.70; p-trend=0.01) and with body mass index <25 kg/m2 (HR, 2.44, 1.25–4.76; p-trend=0.02).
“The biological mechanism linking longer telomere to pancreatic cancer is unclear,” said researchers. Longer telomeres, it has been postulated, may improve the proliferative capacities of a cell and may promote cell division.
“Each round of genome replication has the potential to introduce genetic mutations and chromosomal alterations, which may promote malignant transformation,” they noted. “Furthermore, peripheral blood leukocyte telomere length may serve as an indicator of other factors for pancreatic cancer risk.”
Future efforts should focus on more clearly elucidating the biological mechanisms linking longer telomere lengths to the risk of pancreatic cancer, researchers added.