MOLECULAR-GENETIC ANALYSIS OF EXON-1 TO EXON-6 OF THE APC GENE IN NONPOLYPOSIS FAMILIAL COLORECTAL-CANCER

Familial adenomatous polyposis coli is caused by constitutional mutati ons in the APC gene. The hallmark of familial adenomatous polyposis co li is the presence of numerous (>100) colorectal polyps, but mutations in the 5' end of the APC gene have been associated with familial colo rectal cancer without florid polyposis. Although familial adenomatous polyposis coli accounts for only a minority of familial colorectal can cer cases, we hypothesised that APC: mutations which were not associat ed with florid polyposis might make a significant contribution to nonp olyposis familial colorectal cancer. Tn investigate this possibility, we analysed 40 unrelated patients with familial colorectal cancer with out classical familial adenomatous polyposis coli for mutations in exo ns 1 to 6 (codons 1 to 243) of the APC gene. No mutations were detecte d, but a C-->T polymorphism at nucleotide 333 (Arg-->Trp at codon 99) was identified. No 5' APC mutations were detected in two patients with desmoid tumours and a family history of colorectal cancer and polyps. We conclude that mutations in exons 1 to 6 of the APC gene are infreq uent in patients with familial colorectal cancer who do not have many colorectal polyps.