Plasma 25-Hydroxyvitamin D and Risk of Pancreatic Cancer

Background: Laboratory studies suggest that vitamin D may inhibit pancreatic cancer cell growth. However, epidemiologic studies of vitamin D and pancreatic cancer risk have been conflicting. Methods: To determine whether prediagnostic levels of plasma 25-hydroxyvitamin D (25[OH]D; IDS Inc.; enzyme immunoassay) were associated with risk of pancreatic cancer, we conducted a pooled analysis of nested case-control studies with 451 cases and 1,167 controls from five cohorts through 2008. Median follow-up among controls was 14.1 years in Health Professionals Follow-Up Study (HPFS), 18.3 years in Nurses' Health Study (NHS), 25.3 years in Physicians' Health Study (PHS), 12.2 years in Women's Health Initiative-Observational Study (WHI), and 14.4 years in Women's Health Study (WHS). Logistic regression was used to compare the odds of pancreatic cancer by plasma level of 25(OH) D. Results: Mean plasma 25(OH) D was lower in cases versus controls (61.3 vs. 64.5 nmol/L, P = 0.005). In logistic regression models, plasma 25(OH) D was inversely associated with odds of pancreatic cancer. Participants in quintiles two through five had multivariable-adjusted ORs (95% confidence intervals) of 0.79 (0.56-1.10), 0.75 (0.53-1.06), 0.68 (0.48-0.97), and 0.67 (0.46-0.97; P(trend) = 0.03), respectively, compared with the bottom quintile. Compared with those with insufficient levels [25[OH] D, < 50 nmol/L], ORs were 0.75 (0.58-0.98) for subjects with relative insufficiency [25[OH] D, 50 to <75 nmol/L] and 0.71 (0.52-0.97) for those with sufficient levels [25[OH] D, >= 75 nmol/L]. No increased risk was noted in subjects with 25(OH) D >= 100 nmol/L, as suggested in a prior study. In subgroup analyses, ORs for the top versus bottom quartile of 25(OH) D were 0.72 (0.48-1.08) for women, 0.73 (0.40-1.31) for men, and 0.73 (0.51-1.03) for Whites. Conclusions: Among participants in five large prospective cohorts, higher plasma levels of 25(OH) D were associated with a lower risk for pancreatic cancer. Impact: Low circulating 25(OH) D may predispose individuals to the development of pancreatic cancer. Cancer Epidemiol Biomarkers Prev; 21(1); 82-91. (C) 2011 AACR.