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

Abstract

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 1052 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 odds ratios (OR) 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 standard deviation OR=0.67, 95% CI 0.54, 0.84, p-interaction=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, p-interaction=0.009). Total adiponectin was not associated with PDA in nonsmokers or current smokers. Conclusion 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 explain associations in non-smokers. Impact Future studies of these biomarkers and PDA should examine results by smoking status.

Obesity and Pancreatic Cancer: Insight into Mechanisms

“…A case-control study showed no association of adiponectin with PDAC risk overall; however, higher adiponectin levels were associated with a reduction in PDAC risk among never smokers [111]. An influence of smoking on the risk of adiponectin on PDAC risk has been reported [112]. However, a Mendelian randomization study did not find an association of adiponectin with PDAC risk [93].…”

The Role of Circulating Protein and Metabolite Biomarkers in the Development of Pancreatic Ductal Adenocarcinoma (PDAC): A Systematic Review and Meta-analysis

“…Michaud and colleagues reported a positive association that was stronger among nonsmokers, and this was seen only in nonfasting blood samples ( 25 ). On the other hand, the study by Nogueira and colleagues found an inverse association between plasma C-peptide levels and PDAC risk in current smokers and no association in never or former-smokers ( 26 ). These results indicate that the association of C-peptide levels with PDAC risk is somewhat dependent on smoking status, but further investigation into its role in PDAC development is required.…”

“…5A ) and also showed a certain degree of heterogeneity. Interestingly, like C-peptide levels, two studies reported an inverse association between circulating levels of adiponectin and PDAC risk, which was specific to never smokers ( 26, 47 ). We also identified two studies that looked at the association between another adipokine, leptin and PDAC risk and one of them reported no clear overall association ( 48 ), whereas the second study by Babic and colleagues found higher levels of leptin, indicating an increased risk in men but not in women ( 49 ).…”

Research Progress of C-Peptide and Its Physiological Function

“…), thereby preventing vascular leakage [40]. Research by Nogueira et al Showed that C-peptide levels are inversely related to pancreatic duct adenocarcinoma in current smoking patients [41].…”