Folate intake and breast cancer prognosis: a meta-analysis of prospective observational studies

Some studies have investigated the association between folate intake and breast cancer prognosis, but the results have been far from conclusive. Thus, a meta-analysis was carried out to explore this association. We performed a comprehensive search of the PubMed, Web of Knowledge, and Cochrane databases from inception to May 2013. The summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a random effects model. Prespecified stratified analyses, sensitivity analyses, and dose-response analysis were also carried out. Five studies, with a total of 7299 participants, were included in the meta-analysis. The pooled HR (95% CI) of the five studies on the association of dietary folate intake (highest vs. lowest) with all-cause mortality was 0.74 (0.60-0.92). Stratified analyses suggested that the inverse association of dietary folate and all-cause mortality was more easily detected in studies that focused on prediagnosis diets, included more patients (>1000), had longer follow-up periods (>7 years), used structured interviews, or had more categories of folate intake (>3). However, none of these differences was statistically significant. No significant association was found between total (dietary and supplementary) folate intake and all-cause mortality, or dietary folate intake and breast cancer-specific mortality, with pooled HRs (95% CI) of 0.93 (0.75-1.15) and 0.79 (0.61-1.01), respectively. Sensitivity analyses confirmed the robustness of the findings by excluding studies that poorly represented the cohort. Our findings suggest a significant inverse association between dietary folate intake and all-cause mortality, but not between total folate intake and all-cause mortality.