Breast & Prostate Cancer & Hormone-Related Gene Variants

胸部

• 批准号: 7097455
• 负责人: David John HUNTER
• 金额: $ 127.18万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-03 至 2007-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7097455
• 关键词: apoptosis; breast neoplasms; cancer risk; cell cycle; clinical research; cooperative study; disease /disorder etiology; ethnic group; gene environment interaction; genetic polymorphism; genetic screening; genetic susceptibility; genotype; hormone related neoplasm /cancer; human subject; insulinlike growth factor; interdisciplinary collaboration; lifestyle; mass spectrometry; neoplasm /cancer genetics; nucleic acid sequence; polymerase chain reaction; prostate neoplasms; questionnaires; statistics /biometry; steroid hormone metabolism

DESCRIPTION (provided by applicant): This application is one of four submitted concurrently to allow large-scale analyses of breast and prostate cancer risk in relation to genetic polymorphisms and gene-environment interactions that affect hormone metabolism. These proposals combine the resources of six large prospective cohorts from the American Cancer Society (CPS-II study), Harvard University (Harvard Cohort Studies), the IARC (EPIC study), and the Universities of Hawaii and Southern California (Multiethnic cohort); in addition, two NCI intramural cohorts (PLCO and ATBC studies) will participate. The proposed study is unique in having prospective plasma samples, genetic material, anthropometric measurements, and extensive questionnaire data on diet, physical activity, exogenous hormone use, smoking, and other lifestyle factors from over 790,000 men and women. Because of the scope and collaborative nature of this consortium, simultaneous investigation of genetic predisposition and lifestyle factors is possible, to clarify the inter-relationships between, and the relative importance of, genetic and hormonal risk factors. Specifically, this study will define SNPs and haplotypes in steroid hormone metabolizing genes, genes in the IGF pathway, and related receptor proteins. These candidate genes will be resequenced in 96 cases of advanced breast cancer, and 96 cases of advanced prostate cancer, chosen from the European, African, Latino, Japanese, and Hawaiian-origin ethnic groups. Haplotype tag SNPs will be selected after genotyping of a larger number of SNPs from a collection of 768 samples from the multigenerational CEPH (Centre d'Etude du Polymorphisme Humain) pedigrees and human diversity collection, by the Whitehead Institute for Genome Research and CEPH, and will rapidly be made publicly available. The interaction of genetic variants with hormonal, lifestyle and anthropometric factors known to be associated with breast and prostate cancer will be examined. In a subset of studies, the association of these variants with markers of breast and prostate cancer risk (i.e. plasma steroid hormone levels and IGF-1 levels) will be investigated. Projects developed within the Cohort Consortium will foster continuing interactions between the genomic and epidemiologic research communities and help integrate the rapid advances in genomic research into large-scale epidemiologic studies. The ultimate goal is to provide the foundation for reducing the public health burden of these cancers.

描述（由申请人提供）：此应用程序是同时提交的四个申请之一，允许对遗传性多态性和影响激素代谢的遗传多态性和基因环境相互作用进行大规模分析。这些建议结合了美国癌症协会（CPS-II研究），哈佛大学（哈佛队列研究），IARC（EPIC研究）以及夏威夷大学和南加州大学（多民族同胞）的六个大型前瞻性队列的资源；此外，将参与两个NCI壁内队列（PLCO和ATBC研究）。拟议的研究在拥有前瞻性血浆样本，遗传物质，人体测量以及广泛的饮食，体育锻炼，外源激素使用，吸烟以及其他790,000多名男性和女性的生活方式因素方面是独一无二的。由于该财团的范围和协作性质，可以同时研究遗传易感性和生活方式因素，以阐明遗传和遗传风险因素之间的相互关系以及相对重要性之间的相互关系。具体而言，这项研究将在类固醇代谢基因，IGF途径中的基因和相关受体蛋白中定义SNP和单倍型。这些候选基因将在96例晚期乳腺癌和96例晚期前列腺癌病例中重新置于欧洲，非洲，拉丁美洲裔，日本和夏威夷 - 原始族群。单倍型标签SNP将在基因组研究和人类多样性收集的多代ceph（中心d'Etude du polymormormoriste unain）和人类多样性收集中的768个样本中的大量SNP中进行选择，由基因组研究和CEPH进行了迅速公开提供。将检查遗传变异与已知与乳腺癌和前列腺癌相关的激素，生活方式和人体测量因素的相互作用。在一部分研究中，将研究这些变体与乳腺癌和前列腺癌风险（即血浆类固醇激素水平和IGF-1水平）的关联。在队列联盟内开发的项目将促进基因组和流行病学研究社区之间持续的相互作用，并有助于将基因组研究的快速发展整合到大规模的流行病学研究中。最终目标是为减轻这些癌症的公共卫生负担提供基础。