FAMILIAL COLORECTAL NEOPLASIA LINKED TO CHROMOSOME 9Q222-312

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 结直肠癌是美国成年人癌症死亡的第二大原因。两种常染色体显性遗传性疾病，家族性腺瘤性息肉病和遗传性非息肉病性结直肠癌，加在一起可能占所有病例的5%。然而，在大约20%的额外结肠癌病例中，受影响的个人报告了一级亲属的结肠癌家族史。在对53个家系进行基因组扫描后，其中两个或更多的兄弟姐妹受到65例结肠癌患者的影响，我们使用密集分布的微卫星标记在9号和6号染色体上进行了精细作图。我们在另外70个家族中进一步证实了这些信号，其中9号染色体上的信号强度增加了一个数量级。完成了该区域的SNP分型，并鉴定出单倍型优先在病例中分离，而不是对照。我们目前正在编制复制样本以确认这种关联，并收集更多的家庭成员以确认这种单倍型。此外，我们已经进行了一项带有PGDH基因的SNPs的病例对照研究，并正在为这项研究编写复制样本。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Colorectal cancer is the second most leading cause of cancer death among adult Americans. Two autosomal dominant hereditary forms of the disease, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, together account for perhaps 5%of all cases. However, in about 20% of additional colon cancer cases,the affected individuals report a family history of colon cancer in a first-degree relative. Following a genome scan in 53 kindreds in which 2 or more sibling were affected by 65 with colon cancer, we performed finemapping on chromosomes 9 and 6 using densely spaced microsatellite markers. We further confirmed these signals in an additional 70 kindreds for which signal strength on chromosome 9 was increased by an order of magnitude. SNP typing in this region was completed and identification of a haplotype segregating preferentially in cases, and not controls, as identified. We are currently compiling a replication sample to confirm this association as well as collecting additional family members so as to confirm this haplotype. Additionally, we have performed a case-control study of SNPs with the PGDH gene and are in the process of compiling a replication sample for this study as well.