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Background: B vitamins such as folate, vitamin B6 and vitamin B12 are coenzymes that are essential for DNA methylation and synthesis. Deficiency in these B vitamins may promote tumor carcinogenesis. Studies assessing blood levels of folate, vitamin B6 and vitamin B12 in risk of breast cancer are limited. Methods: We prospectively evaluated plasma levels of folate, Pyridoxal 5’-Phosphate (PLP, the principal active form of vitamin B6), and vitamin B12 in relation to breast cancer risk from 28,345 women in the Women’s Health Study (WHS) aged 45 years or older who provided blood samples and had no history of cancer and cardiovascular disease at baseline in 1993. We included, in the analysis, 850 incident cases of invasive breast cancer identified as of March 31, 2004 and 850 individually matched control subjects. Logistic regression controlling for matching factors as well as other risk factors for breast cancer was used to estimate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two sided. Results: Plasma levels of folate, PLP, and vitamin B12 were not significantly associated with overall risk of breast cancer. Women in the highest quintile group relative to those in the lowest quintile had multiviariate RRs of 1.41 (95% CI=0.99-2.00) for plasma folate (p for trend=0.22), 0.89 (95% CI=0.62-1.29) for plasma PLP (p for trend=0.46), and 1.27 (95% CI=0.90-1.78) for plasma vitamin B12 (p for trend=0.20). The overall associations were not modified by alcohol consumption, supplement use, and follow-up time before/after the fortification of folate in 1998. However, we found a significant inverse association between plasma PLP and breast cancer risk among postmenopausal women; the multivariate RR comparing the highest to the lowest quintile was 0.64 (95% CI=0.42-0.99; p for trend=0.04). We also observed a marginal inverse association between plasma levels of folate and PLP and breast cancer risk in current smokers; the multivariate RRs in the highest quintile group were 0.27 (95% CI=0.07-1.12) for plasma folate (p for trend=0.03), and 0.25 (95% CI=0.06-1.06) for plasma PLP (p for trend=0.06). Conclusions: Plasma levels of B vitamins including folate, vitamin B6, and vitamin B12 are not associated with overall risk of breast cancer. However, higher plasma levels of vitamin B6 may be related to reduced risk of developing postmenopausal breast cancer. The inverse association between plasma folate and vitamin B6 and breast cancer risk among current smokers needs to be confirmed in other large studies.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA