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. This proposal is based on the hypothesis that colorectal cancer (CRC) and other cancers principally occur in a high risk group that is defined by the carriage of specific genes that confer susceptibility to formation of adenomatous colon polyps. Additionally, identification of this group of individuals would lead to a cost effective strategy for reducing CRC mortality by targeting and screening those individuals who are at greatest risk. Genetic susceptibility for the development of CRC is well recognized. While the majority of colon and other cancers are sporadic, there is growing recognition that a significant proportion of cancer is due to inherited susceptibility. It is well established that germline mutations of some of the already known colon cancer susceptibility genes confer a marked risk of early onset colon neoplasia. The ultimate goal of this project is to test the prediction that susceptibility to colon polyp formation is determined by a major susceptibility allele. The goals of the study are: (1) to develop a cohort of 300 adult sibling pairs who are concordant for either colon polyps and/or colon cancer; (2) to perform flexible sigmoidoscopy on up to 600 siblings to determine the presence or absence of colon polyps; (3) to collect whole blood for DNA extraction, white blood cell storage, and serum storage; and (4) to develop polymorphic markers as a pilot project for a small number of candidate gene loci for colon polyp susceptibility. In 2001, the NIH Center for Inherited Disease Research (CIDR) located at Johns Hopkins University approved our study for a 350 marker genome-wide scan. Genotyping work began at CIDR in September 2001. The study investigators also published a paper excluding the COX2 locus as a candidate gene for colon neoplasia.
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