Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3

表征乳腺癌和前列腺癌的遗传易感性；

• 批准号: 7658858
• 负责人: David John HUNTER
• 金额: $ 140.32万
• 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 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7658858
• 关键词: 8q24; Address; Admixture; American Cancer Society; Beta Carotene; Breast; Candidate Disease Gene; Characteristics; Chromosomes; Clinical; Communication; Communities; DNA Resequencing; Data; Data Coordinating Center; Data Set; Databases; Disease; Estrogen receptor negative; Etiology; European; Extraprostatic; Follow-Up Studies; Generations; Genes; Genetic Determinism; Genetic Markers; Genetic Predisposition to Disease; Genetic Variation; Genotype; Gleason Grade for Prostate Cancer; Health; Health Professional; Histopathologic Grade; Indolent; Inherited; International; Investigation; Life Style; Malignant Neoplasms; Malignant neoplasm of prostate; Nurses' Health Study; Pathway interactions; Phase; Physicians; Positioning Attribute; Predisposition; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; Research; Research Infrastructure; Research Personnel; Risk; Risk Factors; Role; Scanning; Single Nucleotide Polymorphism; Staging; Testing; Universities; Woman; Women' s Health; alpha Tocopherol; cancer genetics; cancer prevention; cancer risk; case control; cohort; follow-up; gene discovery; gene environment interaction; genetic risk factor; genome wide association study; genome-wide; malignant breast neoplasm; men; programs; prospective; steroid hormone metabolism; tumor; web site

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.

描述（由申请人提供）：我们建议继续对 NCI 乳腺癌和前列腺癌队列联盟 (BPC3) 进行随访。该联盟成立于过去 4 年，即将完成对类固醇激素代谢和 IGF 途径中超过 70 个候选基因与乳腺癌和前列腺癌风险的评估。获得这些候选基因的重测序和基因分型数据，并选择标签-SNP进行基因分型；研究界可以在公共网站上获取这些数据。超过 7,000 例乳腺癌和超过 8,500 例前列腺癌的基因分型已经完成或即将完成。随着 2007 年中期新增病例的增加，我们预计这些数据库可以扩展到 14,000 个乳腺癌病例和对照，以及 16,000 个前列腺癌病例和对照。从 2005 年开始，NCI 癌症 - 易感性遗传标记 (CGEMS) 项目一直在两项 BPC3 研究（PLCO 研究中的前列腺癌和护士健康研究中的乳腺癌）中进行全基因组 SNP 扫描，在 BPC3 的其他研究中，SNP 的复制在扫描中排名靠前。其他全基因组关联研究正在进行中，包括 MEC 中前列腺癌的混合扫描、女性健康中使用混合 DNA 的乳腺癌扫描 倡议 (WHI)，以及在英国剑桥大学进行的乳腺癌扫描。我们建议扩展 BPC3 作为在 CGEMS 扫描以外的扫描中识别的 SNP 的测试集，并检查 CGEMS 和其他研究中识别的 SNP 中的基因-环境相互作用。我们还建议利用 BPC3 的大小对雌激素受体阴性 (ER-) 乳腺癌和侵袭性前列腺癌进行全基因组关联研究。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与非侵袭性疾病的遗传风险因素不同。单一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，并在乳腺癌协会联盟 (BCAC) 的 2500 例病例中复制 ER-乳腺癌的研究结果。 BPC3 与 BCAC 的联盟将促进两个最大的研究乳腺癌遗传易感性的研究之间的交流和汇总分析。