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

Abstract

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.

Figure 1

Study-specific and pooled multivariable relative risks (RRs) of pancreatic cancer according to highest vs lowest quintile of dietary folate intake. The solid squares and horizontal lines correspond to the study-specific multivariable RRs and 95% confidence intervals (CIs), respectively. The area of the solid square reflects the study-specific weight (inverse of the variance). The open diamond represents the pooled multivariable RR and 95% CI. The dashed vertical line indicates the pooled RR. The solid vertical line indicates a RR of 1.0.

Figure 2

Study-specific and pooled multivariable relative risks (RRs) of pancreatic cancer according to highest vs lowest quintile of total folate intake. The solid squares and horizontal lines correspond to the study-specific multivariable RRs and 95% confidence intervals (CIs), respectively. The area of the solid square reflects the study-specific weight (inverse of the variance). The open diamond represents the pooled multivariable RR and 95% CI. The dashed vertical line indicates the pooled RR. The solid vertical line indicates a RR of 1.0. The Melbourne Collaborative Cohort Study and the Canadian National Breast Screening Study were not included because total folate data were not available in these two studies; the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study and the Netherlands Cohort Study were also excluded because folate intake in these two studies was primarily from or only from diet.