Folate and risk of breast cancer: A meta-analysis

Background Epidemiologic findings are inconsistent concerning risk for breast cancer associated with low folate intake or blood folate levels. We performed a meta-analysis of prospective and case-control studies to examine folate intake and levels in relation to risk of breast cancer. Methods We searched MEDLINE for studies of this association that were published in any language from January 1, 1966, through November 1, 2006. Study-specific risk estimates were pooled by use of a random-effects model. All statistical tests were two-sided. Results Folate intake in increments of 200 mu g/day was not associated with the risk of breast cancer in prospective studies (estimated summary relative risk [RR] = 0.97, 95% confidence interval [CI] = 0.88 to 1.07, for dietary folate [eight studies; 302 959 participants and 8367 patients with breast cancer], and RR = 1.01, 95% CI = 0.97 to 1.05, for total folate [six studies; 306 209 participants and 8165 patients with breast cancer]) but was statistically significantly inversely associated with risk in case-control studies (estimated summary odds ratio [OR] = 0.80, 95% CI = 0.72 to 0.89, for dietary folate [13 studies; 8558 case patients and 10 812 control subjects], and OR = 0.93, 95% CI= 0.81 to 1.07, for total folate [three studies; 2184 case patients and 3233 control subjects]). High blood folate levels versus low levels were not statistically significantly associated with the risk of breast cancer in prospective studies (OR = 0.81, 95% CI = 0.59 to 1.10 [three studies)) or in case-control studies (OR = 0.41, 95% CI = 0.15 to 1.10 [two studies]). Among the two prospective studies and two case-control studies that stratified by alcohol consumption, high folate intake (comparing the highest with the lowest category) was associated with a statistically significant decreased risk of breast cancer among women with moderate or high alcohol consumption (summary estimate = 0.51, 95% CI = 0.41 to 0.63) but not among women with low or no alcohol consumption (summary estimate = 0.95, 95% CI = 0.78 to 1.15). Few studies examined whether the relation between folate intake and breast cancer was modified by intakes of methionine or vitamins B-6 and B-12, and the findings were inconsistent. Conclusion No clear support for an overall relationship between folate intake or blood folate levels and breast cancer risk was found. Adequate folate intake may reduce the increased risk of breast cancer that has been associated with moderate or high alcohol consumption.