Familial adenomatous polyposis: mutation at codon 1309 and early onset of colon cancer

The clinical course of familial adenomatous polyposis (FAP) varies considerably between patients. Prediction of the severity of the disease is important in the interest of effective cancer prevention. We examined whether age at diagnosis of FAP due to gastrointestinal symptoms and age at death due to colorectal cancer are related to the site of mutation in the responsible gene. 225 families with FAP were screened for mutations. The deletion of 5 base pairs at codon 1309 within exon 15 (known to be the most common mutation) was identified in 20 families; other mutations within exons 7-15 were found in 49 families. In patients with the 5 base-pair deletion at codon 1309, gastrointestinal symptoms and death from colorectal cancer occurred about 10 years earlier than in patients with other mutations. The 1309 mutation leads to development of colonic polyps at a younger age, thus giving rise to an earlier malignant transformation. This relationship should be taken into account in strategies for preventing cancer in patients with FAP.