Data from Serum C-peptide, Total and High Molecular Weight Adiponectin, and Pancreatic Cancer: Do Associations Differ by Smoking?

Abstract

<div>Abstract<p><b>Background:</b> 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.</p><p><b>Methods:</b> 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).</p><p><b>Results:</b> 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; <i>P</i><sub>interaction</sub> = 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; <i>P</i><sub>interaction</sub> = 0.009). Total adiponectin was not associated with PDA in nonsmokers or current smokers.</p><p><b>Conclusions:</b> 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.</p><p><b>Impact:</b> Future studies of these biomarkers and PDA should examine results by smoking status. <i>Cancer Epidemiol Biomarkers Prev; 26(6); 914–22. ©2017 AACR</i>.</p></div>