Folate intake and risk of pancreatic cancer: pooled analysis of prospective cohort studies

Bao Y, Michaud DS, Spiegelman D, Albanes D, Anderson KE, Bernstein L, van den Brandt PA, English DR, Freudenheim JL, Fuchs CS, Giles GG, Giovannucci E, Goldbohm RA, Hakansson N, Horn-Ross PL, Jacobs EJ, Kitahara CM, Marshall JR, Miller AB, Robien K, Rohan TE, Schatzkin A, Stevens VL, Stolzenberg-Solomon RZ, Virtamo J, Wolk A, Ziegler RG, Smith-Warner SA (2011) Folate intake and risk of pancreatic cancer: pooled analysis of prospective cohort studies. J Natl Cancer Inst 103:1840-1850

BACKGROUND: Epidemiological studies evaluating the association between folate intake and risk of pancreatic cancer have produced inconsistent results. The statistical power to examine this association has been limited in previous studies partly because of small sample size and limited range of folate intake in some studies. METHODS: We analyzed primary data from 14 prospective cohort studies that included 319,716 men and 542,948 women to assess the association between folate intake and risk of pancreatic cancer. Folate intake was assessed through a validated food-frequency questionnaire at baseline in each study. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random effects model. All statistical tests were two-sided. RESULTS: During 7-20 years of follow-up across studies, 2195 pancreatic cancers were identified. No association was observed between folate intake and risk of pancreatic cancer in men and women (highest vs lowest quintile: dietary folate intake, pooled multivariable RR = 1.06, 95% CI = 0.90 to 1.25, P(trend) = .47; total folate intake [dietary folate and supplemental folic acid], pooled multivariable RR = 0.96, 95% CI = 0.80 to 1.16, P(trend) = .90). No between-study heterogeneity was observed (for dietary folate, P(heterogeneity) = .15; for total folate, P(heterogeneity) = .22). CONCLUSION: Folate intake was not associated with overall risk of pancreatic cancer in this large pooled analysis.