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

Background Patients with X-linked agammaglobulinaemia, a primary immunodefi ciency disorder, suffer from recurrent infections of the respiratory and in testinal tract. Rapidly progressive colorectal cancer was diagnosed in thre e unrelated young adults with X-linked agammaglobulinaemia. This finding im plies a 30-fold increase of risk for this cancer in this patient group. Glu tathione S-transferases are a family of biotransformation enzymes involved in the detoxification of cytotoxic and carcinogenic compounds, that may fun ction in the prevention of carcinogenesis. We investigated the possible rol e of the glutathione S-transferase enzyme system in the apparently increase d colorectal cancer risk in X-linked agammaglobulinaemia patients. Materials and methods We analysed the glutathione levels and the glutathion e S-transferase enzyme activity and iso-enzyme composition in normal coloni c 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 gluta thione S-transferase enzyme activities at all sites in the normal colonic m ucosa as compared to adenoma patients. In X-linked agammaglobulinaemia pati ents 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 agamm aglobulinaemia patients, assuming that detoxification of carcinogenic compo unds plays a role in the aetiology of colon cancer of these patients.