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。该财团已在过去的四年中建立，并且即将在类固醇激素代谢中对> 70个候选基因的评估和IGF途径进行评估。获得了有关这些候选基因的重新衡量和基因分型数据，并选择了用于基因分型的TAG-SNP。这些数据可用于公共网站上的研究社区。在7,000多例乳腺癌病例中进行了基因分型，已完成或即将完成8500例前列腺癌病例。由于到2007年中期，我们预计额外的病例，我们预计这些数据库可以扩展到14,000例乳腺癌的病例和控制，以及16,000例病例和前列腺癌的控制。从2005年开始，NCI癌 - 易感性（CGEM）项目的遗传标志物（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的前列腺癌）中一直在进行BPC3的其他研究中的扫描中，对BPC 3的扫描中的扫描中进行了高度排名。其他全基因组关联研究也正在进行中，包括在MEC中进行前列腺癌的混合扫描，乳腺癌使用妇女健康中的合并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扩展为在扫描以外的扫描中鉴定出的SNP的测试集，并检查在CGEM和其他研究中确定的SNP中的基因环境相互作用。我们还建议利用BPC3的大小来进行全基因组受体阴性（ER-）乳腺癌和攻击性前列腺癌的研究。有证据表明，乳腺癌的病因与ER+乳腺癌的病因不同，同样，侵袭性前列腺癌的遗传危险因素可能与非侵入性疾病的遗传风险因素不同。单个研究没有能力解决这些重要的亚型。在BPC3的其他病例中，我们将复制侵略性前列腺癌的发现，并在乳腺癌协会联盟（BCAC）的2500例病例中复制乳腺癌。 BPC3与BCAC的联盟将促进两项最大的研究组之间的通信和汇总分析，以研究遗传的乳腺癌易感性。