Author
LIN, JENNIFER - BWH & HARVARD, BOSTON | |
LEE, I-MIN - BWH & HARVARD, BOSTON | |
COOK, NANCY - BWH & HARVARD, BOSTON | |
Selhub, Jacob | |
MANSON, JOANN - BWH & HARVARD, BOSTON | |
BURING, JULIE - BWH & HARVARD, BOSTON | |
ZHANG, SHUMIN - BWH & HARVARD, BOSTON |
Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 10/5/2007 Publication Date: 3/1/2008 Citation: Lin, J., Lee, I., Cook, N.R., Selhub, J., Manson, J.E., Buring, J.E., Zhang, S.M. 2008. Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women. American Journal of Clinical Nutrition. 87(3):734-43. Interpretive Summary: This study is about the relationship between B vitamins and the risk of developing breast cancer. In 1993 blood was collected from about 30,000 women who agreed to participate in the Women Health Study which was conducted by members of Harvard University. In 2004 there were 848 cases of breast cancer among the study subjects. We measured the blood vitamins folate, B12 and B6 from these women and compared the data to measurements of blood samples from women who did not develop cancer. The data show that these vitamins confer little or no risk for the development of breast cancer. However very high plasma folate is weakly associated with increased risk of cancer in premenopausal women, whereas lower B6 may increase the risk of developing cancer in postmenopausal women. Technical Abstract: Background: B vitamins such as folate, vitamin B-6, and vitamin B-12 are coenzymes that are important for DNA integrity and stability. Deficiency in these B vitamins may promote tumor carcinogenesis. Objective: We prospectively evaluated plasma concentrations of folate, pyridoxal 5'-phosphate (PLP; the principal active form of vitamin B-6), and vitamin B-12 in relation to breast cancer risk. Design: We included 848 incident cases of invasive breast cancer identified as of March 31, 2004, and 848 individually matched control subjects from 28,345 women in the Women’s Health Study aged >/-45 y who provided blood samples and had no history of cancer and cardiovascular disease at baseline in 1993. Logistic regression controlling for matching factors and other risk factors for breast cancer was used to estimate relative risks (RRs) and 95% CIs. All statistical tests were 2 sided. Results: Plasma concentrations of folate, PLP, and vitamin B-12 were not associated with overall risk of breast cancer. Women in the highest quintile group relative to those in the lowest quintile had multivariate RRs of 1.42(95%CI: 1.00, 2.02) for plasma folate (P for trend= 0.21), 0.91 (95% CI: 0.63, 1.30) for plasma PLP (P for trend = 0.48), and 1.29 (95% CI: 0.92, 1.82) for plasma vitamin B-12 (P for trend = 0.18). However, higher plasma folate concentrations were moderately associated with an increased risk of developing premenopausal breast cancer (P for trend = 0.04) and for developing estrogen receptor (ER)–positive or progesterone receptor (PR)–positive breast tumors (P for trend - 0.06). Conversely, an inverse association was seen between plasma PLP and postmenopausal breast cancer (P for trend = 0.04). Conclusions: Data from this study suggest that B vitamins, including folate, vitamin B-6, and vitamin B-12, may confer little or no reduction in overall risk of developing breast cancer. The observed positive associations of folate status with risk of developing premenopausal breast cancer and ER-positive or PR-positive tumors are unexpected. Additional research is needed to elucidate the role of folate in breast cancer development. |