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Patients with familial adenomatous polyposis (FAP) and age and sex matched controls were tested for cytochrome P4501A2 (CYP1A2), N-acetyltransferase, and xanthine oxidase activities using caffeine urinary metabolites as a discriminator. FAP patients showed significant underactivity of N-acetyltransferase (which inactivates some carcinogens) and significant overactivity of CYP1A2 (which activates some carcinogens). Xanthine oxidase activity, which can generate free radicals and cause cellular damage, was significantly increased in the FAP patients. All but 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. The differences in enzyme activities detected in this study could produce an excess of active carcinogenic metabolites in the bile of FAP patients and contribute to the high risk for intestinal cancer in FAP. (Gut 1995; 36: 251-254 Of the FAP patients, six (21%) were smokers, while 11 (20%) of the controls were smokers. All patients were white with normal liver and kidney function. All but one of the FAP patients had undergone colectomy between 1 and 38 years before sampling. All controls had intact colons.To assess the effect of colectomy on enzyme function, five FAP patients and one patient with ulcerative colitis (average age 24 years, range 17-46; 5 males, 1 female) received analysis of N-acetyltransferase, CYP1A2, and xanthine oxidase activity immediately before colectomy and at a mean time of eight weeks (range 6 to 12) after colectomy.Urine samples were collected at two to six hours after the oral administration of a 300 mg tablet of caffeine (FAP patients) or after a caffeine containing beverage (controls), caffeine intake having been shown not to affect the metabolic profiles obtained.6 Patients were not fasted and were not subject to any dietary restrictions. Ethics committee approval was obtained for this study. Urine samples were stored at -20°C and were later analysed as a single batch.7The caffeine metabolites 1-methyluracil (1-MU), 1-methylxanthine (1-MX), 5-acetylamino-6-amino-3-methyluracil (AAMUwhich is the metabolite of 5-acetylamino-6-formylamino-3-methyluracil (AFMU)) were assayed in the urine samples by a modification of the method of Grant et al.

SummaryTo test whether the presence of gastric adenomas (dysplasia) was associated with gastric reflux of duodenal contents, six patients with familial adenomatous polyposis (FAP) who had gastric adenomas and nine matched FAP patients without gastric adenomas underwent scintigraphic duodeno-gastric reflux scanning. Reflux was graded 0-6, where O=no reflux, l=intermittent reflux into antrum only, 2=prolonged reflux into antrum only, 3=intermittent reflux into body, 4=prolonged reflux into body, 5=intermittent reflux into body and fundus, and 6=prolonged reflux into body and fundus. FAP patients with gastric adenomas had more severe reflux (median 6, range 4-6) than did controls (median 3, range 0-6; P=0.009, Mann-Whitney U test). These results are consistent with a role for bile in the development of gastric adenomatous polyps and suggest that bile is involved in the dysplasiacarcinoma sequence.