Background: Studies examining associations between circulating concentrations of
C-peptide and total
adiponectin, two
biomarkers related to
obesity and insulin secretion and sensitivity and pancreatic ductal
adenocarcinoma (PDA) risk have shown inconsistent results and included limited numbers of smokers.Methods: We examined associations of these
biomarkers and high molecular weight (HMW)
adiponectin with PDA, overall, and by smoking status. We conducted a pooled nested case-control analysis in 3 cohorts (Prostate, Lung, Colorectal, and
Ovarian Cancer Trial,
Alpha-Tocopherol,
Beta-Carotene Cancer Prevention Study, and
Cancer Prevention Study-II), with 758 cases (435 current smokers) and 1,052 controls (531 smokers) matched by cohort, age, sex, race, blood draw date and follow-up time. We used conditional logistic regression adjusted for age, smoking, diabetes, and body mass index to calculate
ORs and 95% confidence intervals (CI).Results: Circulating
C-peptide concentration was not associated with PDA in never or former smokers, but was inversely associated with PDA in current smokers (per SD OR = 0.67; 95% CI, 0.54-0.84; Pinteraction = 0.005). HMW
adiponectin was inversely associated with PDA in never smokers (OR = 0.43; 95% CI, 0.23-0.81), not associated in former smokers, and positively associated in smokers (OR = 1.23; 95% CI, 1.04-1.45; Pinteraction = 0.009). Total
adiponectin was not associated with PDA in nonsmokers or current smokers.Conclusions: Associations of
biomarkers of insulin secretion and sensitivity with PDA differ by smoking status. Smoking-induced pancreatic damage may explain the associations in smokers while mechanisms related to
insulin resistance associations in nonsmokers.Impact: Future studies of these
biomarkers and PDA should examine results by smoking status.
Cancer Epidemiol
Biomarkers Prev; 26(6); 914-22. ©2017 AACR.