| Recently, folate deficiency has been implicated in the development of cancer. The mechanism by which folate is protective is not clear; however there is clear indication that folate plays a role in the synthesis of nucleic acids and the methylation of cytosines in DNA. Four one-carbon gene polymorphisms were examined to determine if they had a modifying effect on diet and breast cancer. The hypermethylation status of the promoter regions of several genes and the estrogen receptor status of all tumors were also determined. Odds ratios and 95% confidence intervals, calculated by unconditional logistic regression, were used to determine if diet and some polymorphic genes predisposed women to breast cancer, p16 hypermethylation and estrogen receptor negative tumors. Our data was consistent with an increased breast cancer risk for postmenopausal women with the MTHFR C677T polymorphism particularly those that consumed inadequate amounts of folate, vitamin B6 and B12, and increased alcohol consumption. MS A2756G was associated with a decreased risk for breast cancer among premenopausal women. We did not detect any risk associated with MTHFR A 1298C or CBS 844ins68. There was no evidence of an interaction between these polymorphisms and p53 mutations, p16 hypermethylation and estrogen receptor status. In conclusion, one-carbon metabolism and polymorphic one-carbon genes have important roles in breast carcinogenesis. |
