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）：该申请是同时提交的四份申请之一，允许对影响激素代谢的遗传多态性和基因-环境相互作用相关的乳腺癌和前列腺癌风险进行大规模分析。这些建议结合了来自美国癌症协会（CPS-II研究）、哈佛大学（哈佛队列研究）、国际癌症研究机构（EPIC研究）和夏威夷大学和南加州大学（多种族队列）的六个大型前瞻性队列的资源；此外，两个NCI内部队列（PLCO和ATBC研究）将参与。这项研究的独特之处在于，它收集了来自79万多名男性和女性的前瞻性血浆样本、遗传物质、人体测量数据，以及关于饮食、体育活动、外源性激素使用、吸烟和其他生活方式因素的广泛问卷数据。由于该联盟的范围和合作性质，同时调查遗传易感性和生活方式因素是可能的，以澄清遗传和激素风险因素之间的相互关系及其相对重要性。具体来说，本研究将确定类固醇激素代谢基因、IGF通路基因和相关受体蛋白的snp和单倍型。这些候选基因将在96例晚期乳腺癌患者和96例晚期前列腺癌患者中进行重新测序，这些患者分别来自欧洲、非洲、拉丁美洲、日本和夏威夷裔人种。单倍型标签snp将在Whitehead基因组研究所和CEPH对来自多代CEPH （Centre d’etude du Polymorphisme human）谱系和人类多样性收集的768个样本进行基因分型后选出，并将迅速公开。基因变异与激素、生活方式和已知与乳腺癌和前列腺癌相关的人体测量因素的相互作用将被检查。在一部分研究中，将调查这些变异与乳腺癌和前列腺癌风险标志物（即血浆类固醇激素水平和IGF-1水平）的关系。在队列联盟内开发的项目将促进基因组和流行病学研究界之间的持续互动，并帮助将基因组研究的快速进展整合到大规模流行病学研究中。最终目标是为减轻这些癌症的公共卫生负担奠定基础。