GENETIC LINKAGE IN COLORECTAL CANCER FAMILES

结直肠癌家族中的遗传连锁

• 批准号: 7125602
• 负责人: JOHN D POTTER
• 金额: $ 73.17万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-20 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125602
• 关键词: African American; Japanese; biotechnology; caucasian American; clinical research; colorectal neoplasms; computer program /software; cooperative study; family genetics; gene expression; gene mutation; genetic markers; genetic screening; genetic susceptibility; genotype; human genetic material tag; human subject; interview; linkage mapping; neoplasm /cancer genetics; racial /ethnic difference; serial analysis of gene expression; statistics /biometry

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is a common, serious disease that clusters in families, such that individuals with an affected sibling are at almost 3-fold increased risk compared to those in the general population. Little, if any, of the observed familial clustering has yet been explained by shared environmental exposures. Known genetic syndromes such as hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) are thought to account for less than 2% of cases. Unidentified susceptibility loci are probably important in much of the remaining non-syndromic familial colorectal cancer. We aim to identify novel CRC susceptibility loci collected via the Colon Cancer Cooperative Family Registry (Colon CFR). The Colon CFR is an NCI-supported consortium initiated in 1997 that has established a comprehensive collaborative infrastructure for interdisciplinary studies in CRC genetic epidemiology. Six cooperating registries have collected CRC tumor specimens, blood samples, and epidemiologic information from multiple-case families. Recruited CRC families from the Colon CFR, as well as from an additional site using identical protocols, who are not shown to carry HNPCC- or FAP-predisposing mutations will be included in a two-stage gene-mapping strategy. First, we will perform a genome-wide linkage analysis using 844 affected relative pairs in 499 families. Approximately 400 microsatellite markers will be genotyped and assessed for evidence of linkage to CRC using parametric and non-parametric methods; regions will be identified for follow-up. Second, individuals from 499 families will be genotyped using more densely-spaced microsatellite markers in genomic regions suggested by the initial scan. Parametric and non-parametric linkage methods will assess evidence for CRC linkage. Strengths of this effort include the use of an existing CRC family collection, a wealth of preliminary data (including screening for known mutations), and a successful collaborative history among investigators. A key future aim is to combine these families with those of other CRC linkage studies in the US and UK to amass an extensive resource with further increased power to understand CRC genetic susceptibility.

描述（由申请人提供）：结直肠癌（CRC）是一种常见的严重疾病，在家庭中群中簇，使患有兄弟姐妹的人与普通人群相比，风险增加了近3倍。几乎没有（如果有的话）在观察到的家族聚类中尚未通过共同的环境暴露来解释。 已知的遗传综合征，例如遗传性非多型结直肠癌（HNPCC）和家族性腺瘤性息肉病（FAP），占病例的不到2％。在其余的许多非综合性家族肠癌中，身份不明的敏感性基因座可能很重要。 我们旨在确定通过结肠癌合作家族登记中心（Colon CFR）收集的新型CRC敏感性基因座。结肠CFR是1997年启动的NCI支持的财团，该联盟已建立了CRC遗传流行病学跨学科研究的全面协作基础设施。六个合作的注册表已收集了来自多案例家族的CRC肿瘤标本，血液样本和流行病学信息。从结肠CFR招募的CRC家族以及使用相同的方案的其他站点，这些招募者未显示出携带HNPCC-或FAP较高的突变突变，​​将包括在两阶段的基因映射策略中。 首先，我们将使用499个家庭中的844个受影响的相对对进行全基因组链接分析。使用参数和非参数方法，将对大约400个微卫星标记进行基因分型和评估，以证明与CRC连接的证据；将确定区域进行后续行动。 其次，使用初始扫描建议的基因组区域中，将使用来自499个家庭的个体进行基因分型。参数和非参数链接方法将评估CRC链接的证据。 这项工作的优势包括使用现有的CRC家庭收集，大量的初步数据（包括筛选已知突变）以及研究人员之间成功的合作历史。未来的关键目的是将这些家庭与美国和英国其他CRC连锁研究的家庭相结合，以积累广泛的资源，并进一步增加了了解CRC遗传易感性的能力。