The presymptomatic molecular diagnosis of familial adenomatous polyposis in Singapore.

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder which predisposes to the development of colorectal cancer. The adenomatous polyposis coli (APC) gene, mutation of which is responsible for FAP, has been localised to chromosome 5q21. Linkage studies using DNA markers have proven useful for presymptomatic diagnosis of at-risk individuals. We have examined 8 FAP families from the Singapore Polyposis Registry by using 4 linked and 2 intragenic DNA markers. Presymptomatic diagnosis could be made in 84% (37 of 44) of at-risk individuals. Among these presymptomatically diagnosed cases, positive prediction was made in 32% (12 of 37) whereas negative prediction was possible in 68% (25 of 37). As the accuracy of genetic diagnosis is high and the test reliable in most cases, the major impact of these tests will be the reduction of unnecessary anxiety and a significant reduction in the frequency of screening for at-risk individuals who are not carrying the affected gene.