title: 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 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.
authors.affiliation: Texas Cancer Registry, Department of State Health Services, Austin, Texas.|Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Rockville, Maryland.
authors.forename: Leticia M
authors.initials: LM
authors.lastname: Nogueira
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta Georgia.
authors.forename: Christina C
authors.initials: CC
authors.lastname: Newton
authors.affiliation: Department of Oncology, Lady Davis Research Institute of the Jewish General Hospital and McGill University, Montreal, Quebec, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Rockville, Maryland.
authors.forename: Debra T
authors.initials: DT
authors.lastname: Silverman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Rockville, Maryland.
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.affiliation: Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Männistö
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Rockville, Maryland.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta Georgia. rs221z@nih.gov Eric.jacobs@cancer.org.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jacobs
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Rockville, Maryland. rs221z@nih.gov Eric.jacobs@cancer.org.
authors.forename: Rachael Z
authors.initials: RZ
authors.lastname: Stolzenberg-Solomon
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000368:Aged; D002096:C-Peptide / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000473:pathology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000097:blood*
chemical_list: D052242:Adiponectin; D002096:C-Peptide