This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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