FAMILIAL COLORECTAL NEOPLASIA LINKED TO CHROMOSOME 9Q222-312

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 结直肠癌是美国成年人癌症死亡的第二大原因。家族性腺瘤性息肉病和遗传性非息肉病性结直肠癌这两种常染色体显性遗传形式的疾病可能占所有病例的5%。然而，在大约20%的额外结肠癌病例中，受影响的个体报告了一级亲属的结肠癌家族史。在对53例有2个或多个兄弟姐妹受65例结肠癌影响的患者进行基因组扫描后，我们使用密集分布的微卫星标记对9号和6号染色体进行了精细定位。 我们进一步证实了这些信号在额外的70 kinetron的信号强度增加了一个数量级的染色体9。 完成了该区域的SNP分型，并确定了在病例中优先分离的单倍型，而不是对照。 我们目前正在编制一个复制样本，以确认这种关联，以及收集更多的家庭成员，以确认这种单倍型。 此外，我们还对PGDH基因的SNP进行了病例对照研究，并正在为这项研究编制复制样本。

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.