The Colon Cancer Family Registry: Seattle

结肠癌家族登记处：西雅图

基本信息

批准号：
7838961
负责人：
POLLY A NEWCOMB
金额：
$ 6.28万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-07-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7838961
关键词：
Administrative Coordination Affect Alleles Ancillary Study Area Australia BRAF gene Behavioral Bioinformatics Blood Blood specimen Budgets Canada Cancer Family Child Chromosome Mapping Clinic Clinical Clinical Data Clinical Management Clinical Research Collaborations Collection Colon Colonoscopy Colorectal Colorectal Cancer Consent DNA DNA Sequence Rearrangement Data Defect Diagnostic Neoplasm Staging Disclosure Economics Elements Enrollment Etiology Family Family Cancer History Family history of Family-Based Registry Funding Future Gene Expression Genes Genetic Genomics Germ-Line Mutation Hypermethylation Idaho Immunohistochemistry Individual Informatics Informed Consent Inherited Interview Joints Lead Lesion MLH1 gene MSH2 gene MSH6 gene Malignant Neoplasms Malignant neoplasm of gastrointestinal tract Medical Genetics Medical Records Medical Research Methylation Mismatch Repair Molecular Monitor Mutation Ontario Operative Surgical Procedures Oregon PMS2 gene Participant Pathology Report Penetrance Persons Phase Policies Polypectomy Prevention Prevention program Procedures Professional counselor Promoter Regions Proteins Protocols documentation Quality Control Queensland Recording of previous events Records Recruitment Activity Recurrent tumor Registries Relative (related person)Research Research Ethics Committees Research Infrastructure Research Institute Research Personnel Resources Risk Risk Factors Sampling Scientist Screening procedure Site Somatic Mutation Source Staging TNM Teleconferences Testing Translational Research Universities Update Vital Status Washington Writing abstracting cancer care cancer genetics cancer prevention cohort colon cancer family registry colorectal cancer screening cost data management data sharing follow-up gene environment interaction genetic epidemiology genetic variant high risk meetings member mortality mutation carrier population based proband programs repository tumor

项目摘要

DESCRIPTION (provided by applicant): The Colorectal Cancer Family Registry - Seattle (CCFR -S), a center within the multinational six-site Colon CFR consortium, is a population-based resource for studies of the genetics and genetic epidemiology of colorectal cancer. We are entering Phase III of this project, the largest ever cohort of colorectal cancer families. In this new application, we propose to continue to expand accrual of individuals with colorectal cancer who carry defective mismatch repair (MMR) alleles or who are at high risk of hereditary colorectal cancer due to other as-yet-unknown genetic variants. To facilitate further analyses of MMR-mutation carriers and to enable investigators to conduct more informative studies, such as those for gene mapping, in Amsterdam families who do not have evidence of an MMR defect, we will enroll families who carry an MMR or MYH mutation and families who meet the Amsterdam criteria without evidence of an MMR mutation (n=80). Probands will be recruited through a collaborative effort with the Gastrointestinal Cancer Prevention Program, an area wide high-risk clinic located at the Seattle Cancer Care Alliance, a joint Fred Hutchinson/UW/Seattle Children's facility. Eligible individuals will complete our standardized family history and risk-factor interview and provide relevant biospecimens: blood (or buccal) samples and tumor blocks. We will support the Molecular Characterization Core activities by submitting participant biospecimen samples for: screening for expression of MLH1, MSH2, and MSH6 proteins; MMR-mutation testing guided by the IHC results; MLH1 methylation testing; screening for selected mutations in MYH; and testing for somatic mutations in BRAF. We will also continue to follow up, using active and passive protocols, our large existing cohort of probands and their relatives to evaluate and monitor: risk of developing new neoplasms; recurrence of original cancer; and mortality from colorectal cancer and other causes. We are currently conducting several ancillary studies focused on: gene hunting; gene-environment interactions; screening efficacy; behavioral changes; issues related to genetic disclosure; and the economics of screening and treatment. This proposal also includes studies to characterize the colorectal lesions that have been collected to date, including germline mutations in MLH1 and MSH2 and hypermethylation of the promoter region of MLH1. The CCFR - S is also responsible for taking the lead in the administrative coordination of all Colon CFR activities, including coordination of protocols and research agendas. Relevance: In collaboration with the other five Colon CFR centers, our registry is a valuable resource for translational research in the genetic epidemiology of colorectal cancer. The CCFR - S provides an important population-based perspective within our consortium studies of colorectal cancer.

描述（由申请人提供）：西雅图结直肠癌家族登记处 (CCFR -S) 是跨国六站点结肠直肠癌联盟的一个中心，是一个基于人群的结直肠癌遗传学和遗传流行病学研究资源。我们正在进入该项目的第三阶段，这是有史以来最大的结直肠癌家族队列。在这项新申请中，我们建议继续扩大携带有缺陷的错配修复（MMR）等位基因或由于其他未知的遗传变异而处于遗传性结直肠癌高风险的结直肠癌患者的治疗范围。为了促进对 MMR 突变携带者的进一步分析，并使研究人员能够在没有 MMR 缺陷证据的阿姆斯特丹家庭中进行更多信息研究，例如基因图谱研究，我们将招募携带 MMR 或 MYH 突变的家庭以及符合阿姆斯特丹标准但没有 MMR 突变证据的家庭 (n=80)。先证者将通过与胃肠癌预防计划的合作来招募，该计划是一个位于西雅图癌症护理联盟的区域性高风险诊所，是 Fred Hutchinson/威斯康星大学/西雅图儿童联合机构。符合条件的个人将完成我们的标准化家族史和危险因素访谈，并提供相关的生物样本：血液（或口腔）样本和肿瘤块。我们将通过提交参与者生物样本来支持分子表征核心活动：筛选 MLH1、MSH2 和 MSH6 蛋白的表达；以 IHC 结果为指导的 MMR 突变测试； MLH1甲基化检测；筛选 MYH 中选定的突变；并测试 BRAF 的体细胞突变。我们还将继续使用主动和被动方案跟踪我们现有的大量先证者及其亲属，以评估和监测：发生新肿瘤的风险；原发癌症复发；以及结直肠癌和其他原因造成的死亡率。我们目前正在进行几项辅助研究，重点是：基因狩猎；基因-环境相互作用；筛选功效；行为改变；与基因披露相关的问题；以及筛查和治疗的经济性。该提案还包括迄今为止收集的结直肠病变特征研究，包括 MLH1 和 MSH2 的种系突变以及 MLH1 启动子区域的高甲基化。 CCFR - S 还负责领导所有 Colon CFR 活动的行政协调，包括协议和研究议程的协调。相关性：通过与其他五个结肠 CFR 中心合作，我们的注册中心是结直肠癌遗传流行病学转化研究的宝贵资源。 CCFR - S 在我们的结直肠癌联合研究中提供了重要的基于人群的视角。