Effects of Folate on the Development of Breast Cancer in a Chemical Rodent Model of Mammary Carcinogenesis

摘要

Epidemiological studies suggest that dietary folate intake and blood levels of folate are inversely related to breast cancer risk. Because only few modifiable risk factors for breast cancer exist, the role of folate in modifying breast cancer risk merits further consideration. Folate is an ideal agent for chemoprevention of breast cancer. It is a natural vitamin, inexpensive, virtually free of side effects, and possesses biologically plausible mechanisms for cancer prevention. However, folate appears to possess dual modulatory effects on carcinogenesis depending on the timing and dose of folate intervention. Folate deficiency has an inhibitory, whereas folate supplementation has a promoting, effect on progression of established neoplasms. By contrast, folate deficiency in normal tissues predisposes them to neoplastic transformation, and modest levels of folate supplementation suppress, whereas supraphygiologic doses enhance, the development of tumors in normal tissues. Therefore, the potential effect of folate chemoprevention needs to be clearly established in appropriate animal models before folate supplementation can be considered in humans. Given these considerations, this proposal investigates the effects of dietary folate deficiency and supplementation on mammary tumorigenesis and potential molecular and cellular mechanisms by which folate modulates mammary tumorigenesis in the well established carcinogen rat model of breast cancer.