Low levels of colonic glutathione S‐transferase in patients with X‐linked agammaglobulinaemia

Abstract

BACKGROUND: Patients with X-linked agammaglobulinaemia, a primary immunodeficiency disorder, suffer from recurrent infections of the respiratory and intestinal tract. Rapidly progressive colorectal cancer was diagnosed in three unrelated young adults with X-linked agammaglobulinaemia. This finding implies a 30-fold increase of risk for this cancer in this patient group. Glutathione S-transferases are a family of biotransformation enzymes involved in the detoxification of cytotoxic and carcinogenic compounds, that may function in the prevention of carcinogenesis. We investigated the possible role of the glutathione S-transferase enzyme system in the apparently increased colorectal cancer risk in X-linked agammaglobulinaemia patients. MATERIALS AND METHODS: We analysed the glutathione levels and the glutathione S-transferase enzyme activity and iso-enzyme composition in normal colonic biopsies of eight X-linked agammaglobulinaemia patients, 25 patients with a recent history of colonic adenomas and 10 healthy volunteers. RESULTS: X-linked agammaglobulinaemia patients had significantly lower glutathione S-transferase enzyme activities at all sites in the normal colonic mucosa as compared to adenoma patients. In X-linked agammaglobulinaemia patients the rectal glutathione S-transferase enzyme activity was lower than in the proximal colon and significantly lower as compared to controls. CONCLUSION: This lower glutathione S-transferase enzyme activity might play a role in the apparently increased colorectal cancer risk in X-linked agammaglobulinaemia patients, assuming that detoxification of carcinogenic compounds plays a role in the aetiology of colon cancer of these patients.