Breast & Prostate Cancer & Hormone-related Gene Variants

描述(由申请人提供)：这份申请是同时提交的四份申请之一，旨在对乳腺癌和前列腺癌的风险进行大规模分析，这些风险与影响激素新陈代谢的基因多态和基因-环境相互作用有关。这些建议结合了来自美国癌症协会(CPS-II研究)、哈佛大学(哈佛大学队列研究)、IARC(EPIC研究)以及夏威夷大学和南加州大学(多种族队列)的六个大型预期队列的资源；此外，NCI的两个内部队列(PLCO和ATBC研究)将参与其中。这项拟议的研究在拥有来自79万多名男性和女性的预期血浆样本、遗传物质、人体测量和关于饮食、体力活动、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方面是独一无二的。由于该联盟的范围和合作性质，有可能同时调查遗传易感性和生活方式因素，以澄清遗传和荷尔蒙风险因素之间的相互关系和相对重要性。具体地说，这项研究将确定类固醇激素代谢基因、IGF途径基因和相关受体蛋白的SNPs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进行重新测序，这些病例选自欧洲、非洲、拉丁裔、日本和夏威夷裔族群。单倍型标签SNPs将由怀特黑德基因组研究所和CEPH从多代人CEPH(Centre d‘Etude du Polyformisme Humain)家系和人类多样性收集的768个样本中对大量SNPs进行基因分型后选出，并将迅速公开提供。我们将研究基因变异与荷尔蒙、生活方式以及已知与乳腺癌和前列腺癌相关的人体测量因素之间的相互作用。在一个子集的研究中，将调查这些变异与乳腺癌和前列腺癌风险标志(即血浆类固醇激素水平和IGF-1水平)的相关性。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。最终目标是为减少这些癌症的公共卫生负担提供基础。

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.