Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3

描述(由申请人提供)：我们建议继续跟进NCI乳腺癌和前列腺癌队列联盟(BPC3)。该联盟成立于过去4年，即将完成对类固醇激素代谢和胰岛素样生长因子途径中70个候选基因与乳腺癌和前列腺癌风险的评估。获得了这些候选基因的重新测序和基因分型数据，并选择了Tag-SNPs进行基因分型；这些数据可以在公共网站上向研究社区提供。7 000多例乳腺癌和8 500多例前列腺癌的基因分型工作已经完成或即将完成。到2007年年中，随着新增病例的增加，我们预计这些数据库可以扩大到14,000例乳腺癌病例和对照，16,000例前列腺癌病例和对照。从2005年开始，NCI癌症-遗传易感性标记(CGEMS)项目在两项BPC3研究(PLCO研究中的前列腺癌和护士健康研究中的乳腺癌)中进行了全基因组SNP扫描，SNP的复制在BPC3的其他研究中排名靠前。其他全基因组关联研究正在进行中，包括在MEC中进行前列腺癌混合扫描，在妇女健康中使用池DNA进行乳腺癌扫描 倡议(WHI)和剑桥大学(英国)的乳腺癌扫描。我们建议将BPC3扩展为CGEMS扫描以外的扫描中发现的SNPs的测试集，并检查CGEMS和其他研究中发现的SNPs中的基因与环境的相互作用。我们还建议利用BPC3的大小进行雌激素受体阴性(ER-)乳腺癌和侵袭性前列腺癌的全基因组关联研究。有证据表明ER-乳腺癌与ER+乳腺癌的病因不同，同样，侵袭性前列腺癌的遗传风险因素可能不同于非侵袭性疾病。单项研究没有能力解决这些重要的亚型。我们将在BPC3的其他病例中复制侵袭性前列腺癌的研究结果，并从乳腺癌协会联合会(BCAC)复制2500例ER-乳腺癌的研究结果。BPC3与BCAC的联盟将促进两组最大的乳腺癌遗传易感性研究之间的沟通和合并分析。

DESCRIPTION (provided by applicant): We propose to continue follow-up of the NCI Breast & Prostate Cancer Cohort Consortium (the BPC3). This Consortium has been established over the last 4 years, and is nearing completion of the assessment of >70 candidate genes in the Steroid Hormone Metabolism and IGF pathways with respect to risk of breast and prostate cancer. Resequencing and genotyping data on these candidate genes was obtained, and tag-SNPs selected for genotyping; these data are available to the research community on a public website. Genotyping in over 7,000 cases of breast cancer, and over 8,500 cases of prostate cancer has been completed or is nearing completion. With the accrual of additional cases by mid-2007, we expect that these databases can be expanded to 14,000 cases and controls of breast cancer, and 16,000 cases and controls of prostate cancer. Starting in 2005, the NCI Cancer - Genetic Markers of Susceptibility (CGEMS) project, has been conducting genome-wide SNP scans in two of the BPC3 studies (prostate cancer in the PLCO study, and breast cancer in the Nurses' Health Study) with replication forSNPs highly ranked in the scan in the other studies of the BPC3. Other genome-wide association studies are ongoing, including an admixture scan for prostate cancer in the MEC, a breast cancer scan using pooled DNAs in the Womens' Health Initiative (WHI), and a breast cancer scan at the University of Cambridge (UK). We propose to expand the BPC3 to serve as a test set for SNPs identified in the scans other than the CGEMS scan, and to examine gene-environment interactions in the SNPs identified in CGEMS and other studies. We also propose to take advantage of the size of the BPC3 to conduct genome-wide association studies of Estrogen Receptor negative (ER-) breast cancer, and Aggressive Prostate Cancer. There is evidence that ER- breast cancer has a different etiology than ER+ breast cancer, and similarly, the genetic risk factors for Aggressive Prostate Cancer may be different than those for non-Aggressive disease. Single studies do not have power to address these important subtypes. We will replicate findings for Aggressive Prostate Cancer in additional cases from the BPC3, and for ER- breast cancer replicate in 2500 cases from the Breast Cancer Association Consortium (BCAC). The alliance of the BPC3 with the BCAC will facilitate communications and pooled analyses between the two largest sets of studies examining inherited susceptibility to breast cancer.