IngentaConnect Low levels of colonic glutathione S-transferase in patients with ...

Authors: Grubben M.J.A.L.^{1, *}; van den Braak C.C.M.¹; Peters W.H.M.¹; van der Meer J.W.M.¹; Nagengast F.M.¹

Source: European Journal of Clinical Investigation, Volume 30, Number 7, July 2000 , pp. 642-645(04)

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.

Keywords: Colorectal cancer risk; detoxification; glutathione S-transferase; X-linked agammaglobulinaemia

Language: English

Document Type: Research article

Affiliations: 1: University Hospital Nijmegen, the Netherlands *

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