GLUTATHIONE-S-TRANSFERASE MU PHENOTYPE IN PATIENTS WITH FAMILIAL ADENOMATOUS POLYPOSIS AND IN UNAFFECTED CONTROLS

Patients with familial adenomatous polyposis (FAP) are at high risk fo r duodenal tumors, the distribution of which suggests that bile is imp ortant in their development. Studies of the bile of FAP patients sugge st that it contains an excess of active carcinogens. Defective hepatic metabolism of carcinogens might account for these findings. The isozy me glutathione S-transferase mu (GST-mu) plays a major role in the hep atic metabolism of carcinogens. Peripheral blood GST-mu status reflect s hepatic GST-mu status. The concentration of GST-mu was therefore mea sured by enzyme-linked immunosorbent assay of heparinized peripheral b lood samples taken from 31 unrelated patients with FAP and from 38 unr elated control patients. FAP and control patients were matched for age , sex, diet, and smoking status. The median GST-mu concentration (micr ograms per milliliter) was 0.5 (interquartile range, 0 to 11.6) in the FAP group and 8.85 (0.9 to 29.4, p = 0.0013) in the control group. Of the 31 FAP patients, ten had no detectable GST-mu activity compared w ith only one of the 38 controls (p = 0.002), while 71% of FAP patients had GST-mu concentrations less than a supplied positive control, comp ared with 50% of control patients (p = 0.064). Abnormal hepatic metabo lism of carcinogens by GST-mu might contribute to the development of i ntestinal tumors in patients with FAP.