Associations of Telomere Length and Diabetes with Pancreatic Cancer

Abstract

Abstract Risk for pancreatic cancer increases strongly with older age, and diabetic conditions have been consistently associated with pancreatic cancer, although the temporal relation between diabetes and pancreatic cancer remains uncertain. Telomeres are complexes of proteins and hexameric DNA repeats that cap and protect the ends of chromosomes. Telomere length decreases with subsequent cell divisions and the length of telomeres in peripheral blood leukocytes (PBL) has been observed to be shorter with older age, and shorter among cases of several cancer types than in controls. We conducted a hospital-based case-control study with 500 cases of pancreatic cancer, and 1,000 controls without pancreatic cancer (500 diabetic and 500 non-diabetic). We examined associations between PBL telomere length and pancreatic cancer status using generalized additive models (GAM), adjusting for age, body mass index, and gender. We observed significant heterogeneity in the association between PBL telomere length and pancreatic cancer by fasting blood glucose status (P < 0.003). Among those with impaired fasting blood glucose (>100 mg/dL) there was a continuous inverse association between pancreatic cancer and telomere length in the GAM adjusted for age, body mass index, sex, and cigarette smoking status. The adjusted odds ratio for pancreatic cancer comparing the 10th percentile of telomere length (4,184 bp) to the 90th percentile (7,823 bp) was 3.21 (95% C.I. 1.87, 5.52). In contrast, no significant association was found between telomere length and pancreatic cancer status among those with normal fasting blood glucose (OR = 0.67; 95% C.I. 0.39, 1.05; comparing 10th to 90th percentiles). We did not find strong evidence for effect modification of the relation between PBL telomere length and pancreatic cancer by age, gender, or cigarette smoking status. Shorter telomeres in peripheral blood may portend higher risk for pancreatic cancer among those with impaired fasting blood glucose, or may indicate cases who are more likely to have tumors that result in diabetes.