Mitochondrial Haplogroups and Breast Cancer Risk

描述(由申请人提供)： 该项目旨在评估线粒体单倍群对乳腺癌风险的贡献，以及通过体重指数(BMI)、循环抗氧化剂水平、饮酒或吸烟对这种风险的任何修改。这项研究将使用嵌套在护士健康研究中的病例对照设计。1834例乳腺癌患者(在1989-90年至2004年6月1日期间被诊断为乳腺癌)和3051名匹配的对照组已经提取了DNA并可供使用。将对8个线粒体SNPs进行基因分型，将参与者分为9个常见的单倍群。单倍组与乳腺癌风险之间的关联将使用Logistic回归进行评估。由于体重指数、循环中的抗氧化剂水平、饮酒和吸烟都被认为会增加氧化应激，通过这些暴露对线粒体单倍群和乳腺癌风险之间的任何关联的修改将使用统计建模和似然比检验进行评估。护士健康研究的前瞻性和规模为研究基因与环境的相互作用提供了独特而强大的资源。研究线粒体基因组和遗传线粒体因子与环境暴露之间的相互作用是乳腺癌易感性的新方法。观察到的任何关联都将为乳腺癌研究和治疗提供新的令人兴奋的途径，有望降低乳腺癌的发病率和死亡率。该项目将研究一种新的乳腺癌易感标记--线粒体基因组。线粒体是细胞的动力源，因此会产生许多有毒物质，这些物质与包括癌症在内的一系列疾病有关。进一步了解遗传线粒体变异对乳腺癌风险的重要性将有助于未来在筛查和治疗方面的研究，以减轻乳腺癌的负担，使其与公众健康非常相关。

DESCRIPTION (provided by applicant): This project is aimed at evaluating the contribution of mitochondrial haplogroups to breast cancer risk, and any modification of this risk by body mass index (BMI), circulating antioxidant levels, alcohol consumption, or cigarette smoking. This study will use a case-control design nested within the Nurses' Health Study. 1834 breast cancer cases (diagnosed between blood draw in 1989-90 and June 1, 2004) and 3051 matched controls have had DNA extracted and available for use. Eight mitochondrial SNPs will be genotyped to classify the participants into nine common haplogroups. Associations between haplogroups and breast cancer risk will be evaluated using logistic regression. As BMI, circulating antioxidant levels, alcohol consumption, and cigarette smoking have all been hypothesized to increase oxidative stress, modification of any associations between mitochondrial haplogroups and breast cancer risk by these exposures will be evaluated using statistical modeling and likelihood ratio tests. The prospective nature and size of the Nurses' Health Study provide a unique and powerful resource for studying gene and environment interactions. Examining the mitochondrial genome and the interaction between inherited mitochondrial factors and environmental exposures are very novel approaches to breast cancer susceptibility. Any associations observed will provide new and exciting avenues of breast cancer research and treatment, hopefully lowering breast cancer morbidity and mortality. This project will examine a novel breast cancer susceptibility marker, the mitochondrial genome. Mitochondria are the cell's power plant, and as such, generate many toxic substances which are implicated in a wide range of diseases, including cancers. Further understanding of the importance of inherited mitochondrial variation on breast cancer risk will aid future research in screening and treatment to lower the burden of breast cancer, making it very relevant to public health.