Familial adenomatous polyposis coli (APC) is an autosomal dominant disease characterized by the development of hundreds of colonic adenomatous polyps and a 100% risk of subsequent colonic cancer if prophylactic colectomy is not performed. It has been estimated that classic APC, in which at least 100 colonic adenomas are present, is responsible for less than 1% of all colon cancer. Recent studies, however, of families with excess colon cancer and less than 100 polyps (usually 10 - 20) have also implicated the APC gene. Segregation analysis has suggested that even the phenotype of a single adenomatous polyp may have a genetic basis. The APC gene has recently been cloned and mutations identified in affected individuals. Individuals with apparently sporadic colonic cancers can now be screened for germ-line mutations in this gene by the method of single strand conformation polymorphism (SSCP). Normal colonic mucosa has already been collected for this purpose from 100 such individuals along with age-matched controls. This analysis will more accurately determine the proportion of colon cancer due to inherited mutations in APC. Assuming that not all colon cancer is found to be due to germ-line mutations in the APC gene, acquired mutations in this gene in colonic cancer can also be sought. Paraffin blocks from 100 non-polyposis colon cancers are available for DNA extraction and SSCP analysis. This study will thus help to define the role of germ-line and acquired mutations in the APC gene in colon cancer. A significant role for this gene will have diagnostic and therapeutic implications which may ultimately reduce morbidity and mortality due to colon cancer.
