The overall objective of this proposal is to determine the role of inheritance in the development of discrete colorectal adenomatous polyps. Although colorectal cancer is believed to arise from benign adenomatus polyps, very little is known concerning the etiology of these polyps. The proposed investigation is based on the recent finding in this laboratory that discrete adenomatous polyps and colorectal cancers were inherited in a large pedigree. The purpose of this proposal is to investigate whether discrete adenomatous polyp inheritance is found in other pedigrees and to estimate the frequency with which adenomatous polyps occur on the basis of inheritance. The proposal will also investigate the suggestion from the previous study that polyp characteristics may distinguish inherited polyps in pedigrees where polyp clustering occurs. Cosegregation of adenomatous polyps and colorectal cancer will also be examined to further define the polyp cancer relationship. Blood samples will be saved for subsequent linkage studies on pedigrees which prove to be informative. The objectives of the study will be accomplished by examining the prevalence and pedigree distribution of colonic polyps and cancer in a number of pedigrees randomly ascertained on the basis of discrete adenomatous polyps found incidentally. A strict sampling scheme will be followed to avoid bias in determining mode of inheritance. Screening will include a family and medical history, stool guaiac testing, physical examination, and flexible 60 cm proctosigmoidoscopic examination. Standard statistical tests will be used for comparisons. Pedigree analysis will be performed using Pedigree Analysis Package which was developed for the analysis of complex traits. The proposed study will result in better understanding of the inheritance and pathogenesis of colonic adenomatous polyps and colorectal cancer. It will provide pedigrees with well defined phenotypes for future linkage studies. The clarification of inherited factors should also lead to improved guidelines for colorectal cancer screening in appropriate populations.
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