MOLECULAR-GENETIC TESTS AS A GUIDE TO SURGICAL-MANAGEMENT OF FAMILIALADENOMATOUS

Background In familial adenomatous polyposis the only curative treatme nt is colectomy, and the choice of operation lies between restorative proctocolectomy (RPC) and colectomy with ileorectal anastomosis (IRA). The RPC procedure carries a higher morbidity but, unlike IRA, removes the risk of subsequent rectal cancer. Since the course of familial ad enomatous polyposis is influenced by the site of mutation in the polyp osis gene, DNA analysis might be helpful in treatment decisions. Metho ds We evaluated the incidence of rectal cancer in polyposis patients w ho had undergone IRA, and examined whether the requirement for subsequ ent rectal excision because of cancer or uncontrollable polyps was rel ated to the site of mutation. Findings Between 1956 and mid-1995, 225 patients registered at the Netherlands Polyposis Registry had undergon e IRA. In 87 of them, a pathogenetic mutation was detected. 72 patient s had a mutation located before codon 1250 and 15 patients after this codon. The cumulative risk of rectal cancer 20 years after surgery was 12%, and at that time 42% had undergone rectal excision. The risk of secondary surgery was higher in patients with mutations in the region after codon 1250 than in patients with mutations before this codon (re lative risk 2.7, p<0.05). Interpretation On this evidence, IRA should be the primary treatment for polyposis in patients with mutations befo re codon 1250, and RPC in those with mutations after this codon.