JNCI Journal of the National Cancer Institute

JNCI Journal of the National Cancer Institute 2003 95(5):373-380; doi:10.1093/jnci/95.5.373
© 2003 by Oxford University Press

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Journal of the National Cancer Institute, Vol. 95, No. 5, 373-380, March 5, 2003
© 2003 Oxford University Press

ARTICLE

Plasma Folate, Vitamin B₆, Vitamin B₁₂, Homocysteine, and Risk of Breast Cancer

Shumin M. Zhang, Walter C. Willett, Jacob Selhub, David J. Hunter, Edward L. Giovannucci, Michelle D. Holmes, Graham A. Colditz, Susan E. Hankinson

Affiliations of authors: S. M. Zhang, Department of Epidemiology, Harvard School of Public Health, and Division of Preventive Medicine and Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; W. C. Willett, D. J. Hunter, E. L. Giovannucci, Departments of Nutrition and Epidemiology, Harvard School of Public Health, and Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School; J. Selhub, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston; M. D. Holmes, Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School; G. A. Colditz, S. E. Hankinson, Department of Epidemiology, Harvard School of Public Health, and Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston.

Correspondence to: Shumin M. Zhang, M.D., Sc.D., Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115 (e-mail: Shumin.Zhang{at}channing.harvard.edu).

Background: In several epidemiologic investigations, folate intake has appeared to reduce the elevated risk of breast cancer associated with moderate alcohol consumption. However, data relating plasma folate levels to breast cancer risk are sparse. We investigated the association between plasma folate and other vitamins with breast cancer in a prospective, nested case–control study. Methods: Blood samples were obtained during 1989 and 1990 from 32 826 women in the Nurses’ Health Study who were followed through 1996 for the development of breast cancer. We identified 712 breast cancer case patients and selected 712 individually matched control subjects. Dietary information was obtained using food frequency questionnaires given in 1980, 1984, 1986, and 1990. Logistic regression was used to estimate the relative risks (RRs) of breast cancer (after adjustment for potential risk factors), and a generalized linear model was used to calculate the Pearson correlation coefficients between plasma estimates of folate, vitamin B₆, vitamin B₁₂, and homocysteine, and intakes of folate, vitamin B₆, and vitamin B₁₂. All statistical tests were two-sided. Results: The multivariable RR comparing women in the highest quintile of plasma folate with those in the lowest was 0.73 (95% confidence interval [CI] = 0.50 to 1.07; P_trend = .06). The inverse association between plasma folate and breast cancer risk was highly statistically significant among women consuming at least 15 g/day (i.e., approximately 1 drink/day) of alcohol (multivariable RR = 0.11, 95% CI = 0.02 to 0.59 for highest versus lowest quintile) in contrast with that of women consuming less than 15 g/day (multivariable RR = 0.72, 95% CI = 0.49 to 1.05). The multivariable RR comparing women in the highest quintile of plasma vitamin B₆ levels with those in the lowest quintile was 0.70 (95% CI = 0.48 to 1.02; P_trend = .09). Plasma vitamin B₁₂ levels were inversely associated with breast cancer risk among premenopausal women (multivariable RR = 0.36, 95% CI = 0.15 to 0.86 for highest versus lowest quintile) but not among postmenopausal women. Plasma homocysteine was not associated with breast cancer risk. Conclusions: Higher plasma levels of folate and possibly vitamin B₆ may reduce the risk of developing breast cancer. Achieving adequate circulating levels of folate may be particularly important for women at higher risk of developing breast cancer because of higher alcohol consumption.

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