Folate intake, post–folic acid grain fortification, and pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Abstract

Folate plays a critical role in DNA methylation, synthesis, and repair. Several epidemiologic studies suggest that higher folate intake is associated with decreased pancreatic cancer risk. We investigated the association between dietary folate intake and pancreatic cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. Dietary data were collected with the use of a self-administered food-frequency questionnaire (1998-2005). Among the 51,988 male and 57,187 female participants, aged 55-74 y at enrollment, with complete dietary and multivitamin information, 162 men and 104 women developed pancreatic cancer during follow-up (January 1998 to December 2006; median: 6.5 y). We used Cox proportional hazards regression with age as the time metric to calculate hazard ratios (HRs) and 95% CIs. The highest compared with the lowest quartile of food folate was associated with a significantly decreased pancreatic cancer risk among women (> or = 253.3 compared with < or = 179.1 microg/d; HR = 0.47; 95% CI: 0.23, 0.94; P for trend: 0.09) but not among men (> or = 229.6 compared with < or = 158.0 microg/d; HR = 1.20; 95% CI: 0.70, 2.04; P for trend: 0.67; P for interaction by sex: 0.03). There was also a significant inverse trend in risk of pancreatic cancer across increasing quartiles of total folate in women (P for trend: 0.04) but not in men (P for trend: 0.65). Folic acid supplements were not associated with pancreatic cancer. These findings support an association between higher food and total folate intakes and decreased risk of pancreatic cancer in women but not in men.