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Low levels of colonic glutathione S‐transferase in patients with X‐linked agammaglobulinaemia
Author(s) -
M.J.A.L. Grubben,
Claudia C.M. van den Braak,
Wilbert H. M. Peters,
J.W.M. van der Meer,
Fokko M. Nagengast
Publication year - 2000
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2000.00668.x
Subject(s) - glutathione , carcinogen , glutathione s transferase , colorectal cancer , enzyme , carcinogenesis , detoxification (alternative medicine) , glutathione transferase , cancer , biology , gastroenterology , medicine , cancer research , pathology , biochemistry , alternative medicine
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.