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


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.


CONCLUSIONS
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.
Grubben
M J
MJ
University Hospital Nijmegen, the Netherlands. M.Grubben@gastro.AZN.NL
van den Braak
C C
CC
Peters
W H
WH
van der Meer
J W
JW
Nagengast
F M
FM
D000236:Adenoma / Q000201:enzymology / Q000453:epidemiology / Q000473:pathology; D000328:Adult; D000361:Agammaglobulinemia / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D001706:Biopsy; D003106:Colon / Q000201:enzymology* / Q000473:pathology; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000473:pathology; D004789:Enzyme Activation; D008040:Genetic Linkage; D005982:Glutathione Transferase / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D008297:Male; D012307:Risk Factors; D014960:X Chromosome
D005982:Glutathione Transferase