Diet, DNA Repair Genes and Breast Cancer Risk

描述（由申请人提供）：50岁后乳腺癌的发病率急剧上升，因此开展研究，检查表观遗传因素，如营养状况，以及与乳腺癌风险相关的遗传多态性，可能会降低这一人群的发病率和死亡率。有证据表明，特定微量营养素摄入不足可能与基因组不稳定性增加有关，我们提出，与DNA修复基因多态性一起，可能导致癌症风险增加。当前提案的具体目标是：1)评估微量营养素摄入不足（叶酸、维生素b12、维生素B6、类胡萝卜素和维生素C）以及膳食血浆生物标志物（血浆叶酸、维生素b12和磷酸吡哆醛（PLP））与乳腺癌风险之间的关系。2)通过微量营养素摄入（叶酸、维生素B12、维生素B6、类胡萝卜素和维生素C）以及膳食血浆生物标志物（血浆叶酸、维生素B12和PLP）与DNA修复基因、XRCC1、XRCC3和p53多态性之间的相互作用来评估乳腺癌风险。我们假设饮食中微量营养素摄入不足，如叶酸和维生素B12，以及选定DNA修复基因的多态性将与乳腺癌风险增加有关。

DESCRIPTION (provided by applicant): 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.