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© The Author 2007. Published by Oxford University Press.
ARTICLE |
Folate and Risk of Breast Cancer: A Meta-analysis
Affiliations of authors: Division of Nutritional Epidemiology, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (SCL, AW); Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, MA (EG); Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA (EG).
Correspondence to: Susanna C. Larsson, PhD, Division of Nutritional Epidemiology, The National Institute of Environmental Medicine, Karolinska Institutet, PO Box 210, SE-171 77 Stockholm, Sweden (e-mail: susanna.larsson{at}ki.se).
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 µg/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 B6 and B12, 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.
| CONTEXT AND CAVEATS Prior knowledge Reports of the association between risk of breast cancer and folate intake or blood levels have been inconsistent. Study type Meta-analysis of prospective cohort and retrospective case–control studies. Contribution Dietary folate intake was statistically significantly inversely associated with risk of breast cancer in case–control studies but was not associated with risk in prospective studies. Blood folate levels were not associated with risk in either type of study. Implications No clear overall association between folate intake or folate blood levels and breast cancer risk was found. Prospective and retrospective studies can give different estimates for associations between dietary exposures and cancer risk. Limitations Misclassification of folate intake may have been introduced in prospective studies that assessed dietary intake only at baseline because of the folate fortification of flour and cereal-grain products in the United States since 1998. Case-control studies may be affected by inaccurate recall of dietary intake.
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