Mitochondrial Genetic Susceptibility to Breast and Prostate Cancers

线粒体对乳腺癌和前列腺癌的遗传易感性

基本信息

批准号：
8444365
负责人：
Iona C Cheng
金额：
$ 7.45万
依托单位：
CANCER PREVENTION INSTIT OF CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-24 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8444365
关键词：
African American Apoptosis Ascorbic Acid Attention Bioinformatics Biological Biometry Breast Breast Cancer Risk Factor Breast Cancer Treatment Carotenoids Case-Control Studies Cataloging Catalogs Cell physiology Data Development Diagnosis Disease Eating Environmental Risk Factor Epidemiology Fatty acid glycerol esters Funding Gene-Modified Genes Genetic Genetic Predisposition to Disease Genetic Variation Genome Genomics Genotype Goals Hawaiian population Heterogeneity Image Individual Inherited Iron Japanese American Knowledge Latino Lead Malignant Neoplasms Malignant neoplasm of prostate Mammary Neoplasms Minority Mission Mitochondria Mitochondrial DNA Mitochondrial Proteins Nuclear Pathway interactions Phenotype Population Population Heterogeneity Predisposition Prevention Production Prostate Protein Biochemistry Public Health Regulator Genes Research Research Personnel Resources Risk Risk Factors Selenium Smoking Stage Grouping Staging Steroids Subgroup Testing Variant Vitamin E Woman analytical method anticancer research base burden of illness cancer cell cancer epidemiology cancer prevention cancer risk carcinogenesis cohort disorder risk experience genetic association genetic epidemiology genetic risk factor genetic variant genome wide association study genome-wide improved innovation insight interest lipid metabolism lycopene malignant breast neoplasm men mitochondrial dysfunction mitochondrial genome non-genetic public health relevance racial/ethnic difference treatment strategy tumor

项目摘要

DESCRIPTION (provided by applicant): Mitochondria control a number of specialized cellular processes that are essential for energy production, fat metabolism, steroid synthesis, and programmed cell death-pathways that are also critical for carcinogenesis. The goal of this application is to identify mitochondrial genes and their pathways that influence the risks of breast and prostate cancer among a diverse population of African American, Japanese American, Native Hawaiian, Latino and White men and women. We propose in Aim 1 to examine the association between mitochondrial genes and pathways encoded by both the nuclear and mitochondrial genomes for their impact on breast and prostate cancer, utilizing innovative gene set enrichment analysis (GSEA) approaches. Mitochondrial genes and nuclear regulators of mitochondrial activity will be identified from a comprehensive catalog of mitochondrial proteins based on computational genomics, protein biochemistry, and imaging. We will test these mitochondrial genes, leveraging existing nuclear and mitochondrial genome-wide SNP data, from our large case-control studies of breast (2,241 cases, 2,863 controls) and prostate cancer (3,634 cases, 3,713 controls) nested within the Multiethnic Cohort (MEC). Aim 2 will evaluate whether genes are modified by disease sub-groups (stage, grade, ER+/- breast tumors), environmental factors related to mitochondrial activity (smoking, BMI, fat, carotenoids, vitamin C, vitamin E, iron, lycopene and selenium) and susceptibility loci for breast and prostate cancer identified by genome-wide association studies. The strengths of this application include: 1) the use of innovative and sophisticated analytical methods; 2) the strong investigative team; 3) the efficient use of existing genetic and epidemiologic resources; and 4) the scientific and public health significance, especially in regards to understudied minority populations. The knowledge gained by this study may extend our understanding of the underlying genetic factors that contribute to breast and prostate cancers, and may lead to key insight into the biologic pathways of cancer development. The ultimate application of these findings may improve the prevention, diagnosis and treatment of cancers of the breast and prostate.

描述（由申请人提供）：线粒体控制许多对于能量生产，脂肪代谢，类固醇合成和程序性细胞死亡途径至关重要的专门细胞过程，这些过程对致癌作用至关重要。该应用的目的是识别线粒体基因及其途径，这些基因影响非裔美国人，日裔美国人，夏威夷人，拉丁裔和白人男人和女性的多样化人群中乳腺癌和前列腺癌的风险。我们建议在AIM 1中检查核和线粒体基因组对线粒体基因和途径之间对乳腺癌和前列腺癌的影响，利用创新的基因集富集分析（GSEA）方法。线粒体活性的线粒体基因和核调节剂将从基于计算基因组学，蛋白质生物化学和成像的线粒体蛋白的全面目录中鉴定出来。我们将测试这些线粒体基因，利用我们对乳腺癌的大病例对照研究（2,241例，2,863例对照）和前列腺癌（3,634例，3,713例，3,713例，3,713例），利用了现有的核和线粒体基因组范围的SNP数据。 AIM 2将评估基因是否通过疾病亚组（阶段，ER +/-乳腺肿瘤），与线粒体活性有关的环境因素（吸烟，BMI，脂肪，类胡萝卜素，维生素C，维生素E，铁，铁，番茄红素和硒）以及乳腺癌和前列腺癌的研究。该应用的优势包括：1）使用创新和复杂的分析方法； 2）强大的调查团队； 3）有效利用现有的遗传和流行病学资源； 4）科学和公共卫生的意义，尤其是在少数群体研究的方面。这项研究获得的知识可能会扩展我们对有助于乳腺癌和前列腺癌的潜在遗传因素的理解，并可能导致对癌症发展的生物学途径的重要见解。这些发现的最终应用可能会改善乳腺癌和前列腺癌的预防，诊断和治疗。