Incidence of breast cancer rises dramatically after age 50, and therefore conducting research that examines epigenetic factors, such as nutritional status, as well as genetic polymorphisms associated with breast cancer risk may reduce morbidity and mortality in this population. Evidence suggests that inadequate intakes of specific micronutrients may be associated with increased genomic instability, and we propose that in conjunction with DNA repair gene polymorphisms, may lead to increased cancer risks. The specific aims of the current proposal are: 1) To assess the relationship between inadequate micronutrient intakes (folate, vitamin B 12, vitamin B6, carotenoids and vitamin C), as well as, dietary plasma biomarkers [plasma folate, vitamin B 12 and pyridoxal phosphate (PLP)] and breast cancer risk. 2) To estimate breast cancer risk due to the interaction between micronutrient intakes (folate, vitamin B 12, vitamin B6, carotenoids and vitamin C), as well as, dietary plasma biomarkers (plasma folate, vitamin B12 and PLP) and polymorphisms in DNA repair genes, XRCC1, XRCC3 and p53. We hypothesize that inadequate dietary intake of micronutrients, such as folate and vitamin B12, and polymorphisms in the selected DNA repair genes will be associated with increased breast cancer risk. We will use existing dietary, biospecimen and other breast cancer risk factor data available from a population-based study investigating genetic and molecular factors involved in breast cancer etiology. One hundred and ninety one breast cancer cases and 191 sister/cousin controls will be included to measure the association between dietary intake/dietary plasma biomarkers and breast cancer risk. We will use a case-only design of 500 cases diagnosed with breast cancer to assess interactions between dietary intakes of micronutrients involved in folate metabolism, as well as selected antioxidants, and polymorphisms in DNA repair genes, XRCC1, XRCC3 and p53. Investigation of the interactions between dietary intakes/dietary plasma biomarkers and genetic polymorphisms in DNA repair genes will not only more precisely decipher the role of diet in breast cancer etiology, but also add to our understanding of the molecular mechanisms in association with environmental exposures involved in breast cancer. Additionally, the findings of this study will provide directions for future epigenetic investigations, and targeted cancer prevention strategies.