Prediagnostic plasma C-peptide and pancreatic cancer risk in men and women.
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.
Michaud
Dominique S
DS
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. dmichaud@hsph.harvard.edu
Wolpin
Brian
B
Giovannucci
Ed
E
Liu
Simin
S
Cochrane
Barbara
B
Manson
JoAnn E
JE
Pollak
Michael N
MN
Ma
Jing
J
Fuchs
Charles S
CS
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
D014408:Biomarkers, Tumor; D007328:Insulin; D002097:C-Reactive Protein