title: Prediagnostic plasma C-peptide and pancreatic cancer risk in men and women.
abstract: BACKGROUND
  Hyperinsulinemia and insulin resistance have been proposed as underlying mechanisms for the increase in pancreatic cancer among long-standing diabetics and obese individuals. An association between serum insulin levels and pancreatic cancer risk was reported in a recent study, but the population was composed of heavy smokers and their findings may not be generalizable to nonsmokers.
  
  
  METHODS
  Pancreatic cancer cases and matched controls were obtained from four large-scale prospective cohorts to examine the association between prediagnostic plasma levels of C-peptide and insulin and pancreatic cancer. One hundred ninety-seven pancreatic cancer cases were diagnosed during a maximum of 20 years of follow-up, after excluding cases diagnosed within 2 years of blood collection or with baseline diabetes. We estimated OR and confidence intervals (CI) using conditional logistic regression with adjustment for pancreatic cancer risk factors.
  
  
  RESULTS
  Prediagnostic plasma C-peptide was positively associated with pancreatic cancer risk (OR, 1.52; 95% CI, 0.87-2.64, highest compared with the lowest quartile, P(trend) = 0.005). The association was not modified by body mass index or physical activity but seemed to be slightly stronger among never smokers than ever smokers. Fasting C-peptide and insulin were not related to pancreatic cancer; however, we observed a strong linear association for nonfasting C-peptide and pancreatic cancer (OR, 4.24; 95% CI, 1.30-13.8, highest versus lowest quartile, P(trend) < 0.001).
  
  
  CONCLUSIONS
  Based on our finding of a strong positive association with nonfasting C-peptide levels, we propose that insulin levels in the postprandial state may be the relevant exposure for pancreatic carcinogenesis; however, other studies will need to examine this possibility.
authors: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. dmichaud@hsph.harvard.edu
authors: Dominique S
authors: DS
authors: Michaud
authors: Brian
authors: B
authors: Wolpin
authors: Ed
authors: E
authors: Giovannucci
authors: Simin
authors: S
authors: Liu
authors: Barbara
authors: B
authors: Cochrane
authors: JoAnn E
authors: JE
authors: Manson
authors: Michael N
authors: MN
authors: Pollak
authors: Jing
authors: J
authors: Ma
authors: Charles S
authors: CS
authors: Fuchs
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism*; D015444:Exercise / Q000502:physiology; D005215:Fasting / Q000502:physiology; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D019518:Postprandial Period / Q000502:physiology; D011379:Prognosis; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D007328:Insulin; D002097:C-Reactive Protein