Diet, DNA Repair Genes and Breast Cancer Risk

描述(申请人提供)：乳腺癌的发病率在50岁以后急剧上升，因此进行研究，检查表观遗传因素，如营养状况，以及与乳腺癌风险相关的基因多态，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，我们认为，与DNA修复基因多态一起，可能导致癌症风险增加。目前建议的具体目标是：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记物[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)评估因摄入微量营养素(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记物(血浆叶酸、维生素B12和PLP)和DNA修复基因XRCC1、XRCC3和P53多态性之间的相互作用而导致乳腺癌的风险。我们假设膳食摄入不足的微量营养素，如叶酸和维生素B12，以及选定的DNA修复基因的多态性将与乳腺癌风险增加相关。 我们将使用现有的饮食、生物素和其他乳腺癌危险因素数据，这些数据来自一项基于人群的研究，该研究调查了与乳腺癌病因有关的遗传和分子因素。将包括191例乳腺癌病例和191名姐妹/表亲对照，以衡量饮食摄入/饮食血浆生物标记物与乳腺癌风险之间的联系。我们将使用仅病例设计来评估参与叶酸代谢的微量营养素以及选定的抗氧化剂与DNA修复基因XRCC1、XRCC3和P53的多态之间的相互作用。研究膳食摄入量/膳食血浆生物标记物与DNA修复基因遗传多态性之间的相互作用，不仅可以更准确地破译饮食在乳腺癌病因中的作用，而且有助于我们理解乳腺癌与环境暴露相关的分子机制。此外，这项研究的结果将为未来的表观遗传学研究和有针对性的癌症预防策略提供方向。

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.