A prospective study of folate intake and the risk of breast cancer

Shumin Zhang, David J. Hunter, Susan E. Hankinson, Edward L. Giovannucci, Bernard A. Rosner, Graham A. Colditz, Frank E. Speizer, Walter C. Willett

Research output: Contribution to journalArticlepeer-review

377 Scopus citations


Context: Folate is involved in DNA synthesis and methylation and may reduce breast cancer risk, particularly among women with greater alcohol consumption. Objectives: To assess the association between folate intake and risk of breast cancer and whether higher folate intake may reduce excess risk among women who consume alcohol. Design: Prospective cohort study performed in 1980, with 16 years of follow-up. Setting and Participants: A total of 88 818 women who completed the dietary questionnaire section of the Nurses' Health Study in 1980. Main Outcome Measure: Incidence of invasive breast cancer by levels of folate and alcohol intake. Results: A total of 3483 cases of breast cancer were documented. Total folate intake was not associated with overall risk of breast cancer. However, among women who consumed at least 15 g/d of alcohol, the risk of breast cancer was highest among those with low folate intake. For total folate intake of at least 600 μg/d compared with 150 to 299 μg/d, the multivariate relative risk (RR) was 0.55 (95% confidence interval [CI], 0.39-0.76; P for trend = .001). This association was only slightly attenuated after additional adjustment for intake of beta carotene, lutein/zeaxanthin, preformed vitamin A, and total vitamins C and E. The risk of breast cancer associated with alcohol intake was strongest among women with total folate intake of less than 300 μg/d (for alcohol intake ≥15 g/d vs <15 g/d, multivariate RR, 1.32; 95% CI, 1.15-1.50). For women who consumed at least 300 μg/d of total folate, the multivariate RR for intake of at least 15 g/d of alcohol vs less than 15 g/d was 1.05 (95% CI, 0.92- 1.20). Current use of multivitamin supplements, the major source of folate, was associated with lower breast cancer risk among women who consumed at least 15 g/d of alcohol (for current users of supplements vs never users, RR, 0.74; 95% CI, 0.59-0.93). Conclusions: Our findings suggest that the excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake.

Original languageEnglish
Pages (from-to)1632-1637
Number of pages6
Issue number17
StatePublished - May 5 1999


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