BACKGROUND: Epidemiologic evidence supports an association between high folate intake and reduced risk of some cancers, in particular colorectal cancer. However, epidemiologic data concerning the relationship between folate and pancreatic cancer risk are sparse. We examined the association between folate intake and risk of pancreatic cancer in a population-based prospective study of Swedish women and men. METHODS: We prospectively followed 81,922 women and men in the Swedish Mammography Cohort and the Cohort of Swedish Men who were cancer-free and completed a 96-item food-frequency questionnaire in 1997. Cox proportional hazards models were used to estimate multivariable rate ratios (RRs) with 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: A total of 135 incident pancreatic cancer cases were diagnosed during a mean follow-up of 6.8 years. In multivariable analyses controlling for age, smoking, fruit and vegetable consumption, and other potential confounders, dietary and total folate intakes were statistically significantly inversely associated with risk of pancreatic cancer. The multivariable rate ratios of pancreatic cancer for those in the highest category of folate intake (> or = 350 microg/day) compared with the lowest category of intake ( or = 300 microg/day compared with 0 microg/day of supplemental folic acid, multivariable RR = 1.02; 95% CI = 0.56 to 1.88). The sex- and age-standardized incidence rates of pancreatic cancer per 100,000 person-years were 41 for the lowest and 18 for the highest category of dietary folate intake. CONCLUSION: Our results suggest that increased intake of folate from food sources, but not from supplements, may be associated with a reduced risk of pancreatic cancer.