Seattle Colorectal Cancer Family Registry (CFR)

西雅图结直肠癌家族登记处 (CFR)

基本信息

批准号：
7495851
负责人：
POLLY A NEWCOMB
金额：
$ 177.45万
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 2008-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7495851
关键词：
Address Administrative Coordination Affect Age Alleles Ancillary Study Area BRAF gene Behavioral Benefits and Risks Biopsy Blood Cancer Family Child Chromosome Mapping Clinic Clinical Collaborations Colon Colonoscopy Colorectal Colorectal Cancer Data Databases Defect Diagnosis Disclosure Disease Economics Employee Strikes Endometrial Endometrial Carcinoma Enrollment Environmental Risk Factor Etiology Family Family-Based Registry General Population Genes Genetic Genus Cola Germ-Line Mutation Gynecologic Gynecologic Surgical Procedures Hereditary Malignant Neoplasm Hypermethylation Hysteroscopy Immunohistochemistry Incidence Individual Inherited Interview Joints Lead Lesion MLH1 gene MSH2 gene MSH6 gene Malignant Female Reproductive System Neoplasm Malignant Neoplasms Malignant neoplasm of ovary Methylation Mismatch Repair Molecular Monitor Mutation Newly Diagnosed Numbers Operative Surgical Procedures Ovarian Carcinoma PMS2 gene Participant Patients Penetrance Peutz-Jeghers Syndrome Phase Phenotype Population Prevention program Principal Investigator Promoter Regions Proteins Protocols documentation Recruitment Activity Recurrent tumor Registries Relative (related person)Reporting Research Research Personnel Resources Risk Risk Assessment Risk Factors STK11 gene Sampling Screening procedure Series Site Stomach Subgroup Syndrome TP53 gene Testing Translational Research Transvaginal Ultrasound Urinary tract Woman base biliary tract cancer care cancer prevention cancer risk cohort follow-up gastrointestinal gene environment interaction genetic epidemiology genetic variant improved lifetime risk mortality mutation carrier outcome forecast polyposis prevent proband programs prophylactic prospective protein expression tumor

项目摘要

{\rtf1\ansi\ansicpg1252\deff0\deflang1033{\fonttbl{\f0\fswiss\fcharset0 Arial;}} {\*\generator Msftedit 5.41.15.1515;}\viewkind4\uc1\pard\f0\fs21 Project Summary: The Colorectal Cancer Family Registry - Seattle (CCFR -S), a center within the\par multinational six-site Colon CFR consortium, is a population-based resource for studies of the genetics and\par genetic epidemiology of colorectal cancer. We are entering Phase III of this project, the largest ever cohort\par of colorectal cancer families. In this new application, we propose to continue to expand accrual of individuals\par with colorectal cancer who carry defective mismatch repair (MMR) alleles or who are at high risk of\par hereditary colorectal cancer due to other as-yet-unknown genetic variants. To facilitate further analyses of\par MMR-mutation carriers and to enable investigators to conduct more informative studies, such as those for\par gene mapping, in Amsterdam families who do not have evidence of an MMR defect, we will enroll families\par who carry an MMR or MYH mutation and families who meet the Amsterdam criteria without evidence of an\par MMR mutation (n=80). Probands will be recruited through a collaborative effort with the Gastrointestinal\par Cancer Prevention Program, an area wide high-risk clinic located at the Seattle Cancer Care Alliance, a joint\par Fred Hutchinson/UW/Seattle Children's facility. Eligible individuals will complete our standardized familyhistory\par and risk-factor interview and provide relevant biospecimens: blood (or buccal) samples and tumor\par blocks. We will support the Molecular Characterization Core activities by submitting participant biospecimen\par samples for: screening for expression of MLH1, MSH2, and MSH6 proteins; MMR-mutation testing guided by\par the IHC results; MLH1 methylation testing; screening for selected mutations in MYH; and testing for somatic\par mutations in BRAF. We will also continue to follow up, using active and passive protocols, our large existing\par cohort of probands and their relatives to evaluate and monitor: risk of developing new neoplasms; recurrence\par of original cancer; and mortality from colorectal cancer and other causes. We are currently conducting\par several ancillary studies focused on: gene hunting; gene-environment interactions; screening efficacy;\par behavioral changes; issues related to genetic disclosure; and the economics of screening and treatment.\par This proposal also includes studies to characterize the colorectal lesions that have been collected to date,\par including germline mutations in MLH1 and MSH2 and hypermethylation of the promoter region of MLH1.\par The CCFR - S is also responsible for taking the lead in the administrative coordination of all Colon CFR\par activities, including coordination of protocols and research agendas.\par Relevance: In collaboration with the other five Colon CFR centers, our registry is a valuable resource for\par translational research in the genetic epidemiology of colorectal cancer. The CCFR - S provides an important\par population-based perspective within our consortium studies of colorectal cancer.\fs20\par \par }

{\rtf1\ansi\ansicpg1252\deff0\deflang1033{\fonttbl{\f0\fswiss\fcharset0 Arial;}} {\*\generator Msftedit 5.41.15.1515;}\viewkind4\uc1\pard\f0\fs21 项目摘要：结直肠癌家族登记处 - 西雅图 (CCFR -S)，\par 内的一个中心跨国六站点 Colon CFR 联盟，是一个基于人群的遗传学研究资源，\par 结直肠癌的遗传流行病学。我们正在进入该项目的第三阶段，这是有史以来最大的一批\标准结直肠癌家族。在这个新的应用程序中，我们建议继续扩大个人的应计\标准携带有缺陷的错配修复 (MMR) 等位基因或具有高风险的结直肠癌患者由其他未知的基因变异引起的遗传性结直肠癌。为了便于进一步分析\par MMR 突变携带者并使研究人员能够进行更多信息丰富的研究，例如针对\par的研究基因图谱，在阿姆斯特丹没有 MMR 缺陷证据的家庭中，我们将招募家庭\par 携带 MMR 或 MYH 突变的人以及符合阿姆斯特丹标准但没有\par 证据的家庭 MMR 突变 (n=80)。先证者将通过与胃肠道的合作来招募癌症预防计划，一个位于西雅图癌症护理联盟的区域性高风险诊所，该联盟是一个联合\标准 Fred Hutchinson/威斯康星大学/西雅图儿童设施。符合条件的个人将完成我们的标准化家族史\par 和危险因素访谈并提供相关生物样本：血液（或口腔）样本和肿瘤\par 块。我们将通过提交参与者生物样本\par来支持分子表征核心活动样本用于：筛选 MLH1、MSH2 和 MSH6 蛋白的表达； \par 指导下的 MMR 突变测试 IHC 结果； MLH1甲基化检测；筛选 MYH 中选定的突变；并测试体细胞\par BRAF 突变。我们还将继续使用主动和被动协议来跟进我们现有的大型\标准先证者及其亲属队列进行评估和监测：发生新肿瘤的风险；重复\par 原发癌症；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\par 一些辅助研究的重点是：基因狩猎；基因-环境相互作用；筛查功效；\par 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。\par 该提案还包括对迄今为止收集的结直肠病变特征进行的研究，\par 包括 MLH1 和 MSH2 的种系突变以及 MLH1 启动子区域的高甲基化。\par CCFR - S 还负责牵头所有 Colon CFR\par 的行政协调活动，包括协议和研究议程的协调。\par 相关性：通过与其他五个结肠 CFR 中心合作，我们的注册表是\par 的宝贵资源结直肠癌遗传流行病学的转化研究。 CCFR - S 提供了重要的\标准我们的结直肠癌联合研究中基于人群的观点。\fs20\par \par }

项目成果

期刊论文数量（49）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

KRAS-mutation status in relation to colorectal cancer survival: the joint impact of correlated tumour markers.

DOI：
10.1038/bjc.2013.118
发表时间：
2013-04-30
期刊：
British journal of cancer
影响因子：
8.8
作者：
Phipps AI;Buchanan DD;Makar KW;Win AK;Baron JA;Lindor NM;Potter JD;Newcomb PA
通讯作者：
Newcomb PA

Association between molecular subtypes of colorectal cancer and patient survival.

DOI：
10.1053/j.gastro.2014.09.038
发表时间：
2015-01
期刊：
Gastroenterology
影响因子：
29.4
作者：
Phipps AI;Limburg PJ;Baron JA;Burnett-Hartman AN;Weisenberger DJ;Laird PW;Sinicrope FA;Rosty C;Buchanan DD;Potter JD;Newcomb PA
通讯作者：
Newcomb PA

Simulation modeling of outcomes and cost effectiveness.

结果和成本效益的模拟建模。