Abstract : Breast cancer is thought to be largely preventable through dietary and lifestyle modifications. Diets high in vegetables and fruits have been associated with reduced risk of breast cancer in many epidemiologic studies. Minor components of diet such as micronutrients including vitamins may be involved in mediating these associations, but it is not known which micronutrients are involved or how they act. Such knowledge is critical to rationally design and to implement a preventive strategy against breast cancer. Folate, a B vitamin mostly found in vegetables and fruits, may be a protective micronutrient in diet. It is a crucial component in DNA methylation as well as DNA synthesis, both of which are important processes in etiology of breast cancer. Certain genes involved in these processes differ from on person to another. Therefore, a portion of the general population with inherited sub-optimal folate metabolism along with low folate intake may be at increased risk of developing breast cancer. We plan to use a multi-disciplinary approach to study both nutritional and genetic aspects of the disease. We will investigate: (1) whether dietary folate is a micronutrient that is protective against breast cancer; (2) whether a proportion of the population with inherited sub-optimal folate metabolism is at increased risk of breast cancer; (3) whether such inherited variability modifies the association of folate intake and risk of breast cancer; and (4) whether folate may interact with alcohol that interrupts folate metabolism in contributing to risk of breast cancer.

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