title: 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.
  
  
  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.
authors.affiliation: University Hospital Nijmegen, the Netherlands. M.Grubben@gastro.AZN.NL
authors.forename: M J
authors.initials: MJ
authors.lastname: Grubben
authors.forename: C C
authors.initials: CC
authors.lastname: van den Braak
authors.forename: W H
authors.initials: WH
authors.lastname: Peters
authors.forename: J W
authors.initials: JW
authors.lastname: van der Meer
authors.forename: F M
authors.initials: FM
authors.lastname: Nagengast
mesh_terms: 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
chemical_list: D005982:Glutathione Transferase