Mitochondrial Haplogroups and Breast Cancer Risk

线粒体单倍群和乳腺癌风险

• 批准号: 7320200
• 负责人: David G Cox
• 金额: $ 8.75万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7320200
• 关键词: Adenosine Triphosphate; Alcohol consumption; Alcohols; Antioxidants; Apoptosis; Bacteria; Biology; Blood; Body mass index; Cells; Cold Climate; DNA; Data; Diagnosis; Disease; Electron Transport; Environmental Exposure; Eukaryotic Cell; Future; Genetic Polymorphism; Genome; Genotype; Haplogroup; Health; Individual; Inherited; Logistic Regressions; Malignant Neoplasms; Mitochondria; Modification; Morbidity - disease rate; Mutagens; Mutation; Nature; Nurses; Nurses' Health Study; Organelles; Oxidative Stress; Participant; Play; Poison; Population; Power Plants; Predisposition; Production; Public Health; Questionnaires; Range; Reactive Oxygen Species; Research; Resources; Risk; Role; Screening procedure; Single Nucleotide Polymorphism; Smoking; Statistical Models; Testing; Thinking; Variant; anticancer research; cancer risk; case control; cigarette smoking; cohort; day; design; disorder risk; gene environment interaction; interest; malignant breast neoplasm; mitochondrial genome; mortality; novel; novel strategies; prospective; size; steroid hormone; sugar

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.

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。本研究将采用嵌套在护士健康研究中的病例对照设计。1834例乳腺癌病例（在1989-90年和2004年6月1日之间抽血诊断）和3051例匹配的对照已提取DNA并可供使用。将对8个线粒体SNP进行基因分型，以将参与者分为9个常见单倍型组。单倍型群和乳腺癌风险之间的关联将使用逻辑回归进行评估。由于BMI、循环抗氧化剂水平、饮酒和吸烟都被假设为增加氧化应激，因此将使用统计建模和似然比检验评估线粒体单倍型群与这些暴露的乳腺癌风险之间的任何关联。护士健康研究的前瞻性和规模为研究基因和环境的相互作用提供了独特而强大的资源。检查线粒体基因组以及遗传线粒体因子与环境暴露之间的相互作用是研究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，希望降低乳腺癌发病率和死亡率。该项目将研究一种新的乳腺癌易感性标志物，线粒体基因组。线粒体是细胞的发电厂，因此，产生许多与包括癌症在内的广泛疾病有关的有毒物质。进一步了解遗传性线粒体变异对乳腺癌风险的重要性将有助于未来的筛查和治疗研究，以降低乳腺癌的负担，使其与公共卫生非常相关。