CAFFEINE PHENOTYPING OF CYTOCHROME P4501A2, N-ACETYLTRANSFERASE, AND XANTHINE-OXIDASE IN PATIENTS WITH FAMILIAL ADENOMATOUS POLYPOSIS

Patients with familial adenomatous polyposis (FAP) and age and sex mat ched controls were tested for cytochrome P4501A2 (CYP1A2), N-acetyltra nsferase, and xanthine oxidase activities using caffeine urinary metab olites as a discriminator. FAP patients showed significant underactivi ty of N-acetyltransferase (which inactivates some carcinogens) and sig nificant overactivity of CYP1A2 (which activates some carcinogens). Xa nthine oxidase activity, which can generate free radicals and cause ce llular damage, was significantly increased in the FAP patients. All bu t one of the FAP patients had undergone colectomy. A separate group of six patients was therefore assessed before and at an average time of eight weeks after colectomy. No effect on enzyme activity was seen. Th e differences in enzyme activities detected in this study could produc e an excess of active carcinogenic metabolites in the bile of FAP pati ents and contribute to the high risk for intestinal cancer in FAP.