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Prediagnostic Plasma C-Peptide and Pancreatic Cancer Risk in Men and Women

¹ Channing Laboratory, Department of Medicine, and ² Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of ³ Epidemiology and ⁴ Nutrition, Harvard School of Public Health; ⁵ Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; ⁶ Departments of Medicine and Oncology, Lady Davis Research Institute of the Jewish General Hospital and McGill University, Montreal, Canada; ⁷ University of Washington School of Nursing, Seattle, Washington; and ⁸ University of California at Los Angeles School of Public Health, Los Angeles, California

Requests for reprints: Dominique Michaud, Harvard School of Public Health, Kresge 920, 677 Huntington Avenue, Boston, MA 02115. Phone: 617-432-4508; Fax: 617-566-7805. E-mail: dmichaud{at}hsph.harvard.edu

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. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2101–9)