title: A germline homozygote deletion of the glutathione-S-transferase Mu1 gene predisposes to bladder cancer.
abstract: OBJECTIVE
  Numerous studies have shown smoking and specific occupational exposures to be risk factors for bladder cancer. The risk of bladder cancer may be modified by the activity of carcinogen metabolizing enzymes. The glutathione-S-transferase Mu1 enzyme (GSTM1) detoxifies arylepoxides which are formed after exposure to certain polycyclic aromatic hydrocarbons and possibly aromatic amines. Approximately 40% of Caucasians lack GSTM1 activity due to a homozygous deletion of the GSTM1 locus on chromosome 1p13 (GSTM1 0/0 genotype). The aim of this study was to evaluate the combined effect of smoking and GSTM1 genotype on the risk of bladder cancer.
  
  
  METHODS
  Sixty-one patients with transitional cell carcinoma of the bladder and 69 controls matched for age and sex were enrolled from the outpatient clinic. Lifestyle information was collected with a standardized questionnaire. DNA was extracted from white blood cells. The GSTM1 genotype was determined by a PCR-based method.
  
  
  RESULTS
  92% of the 61 patients had a history of smoking compared with 81% of the controls. There was a significant dose-response relationship for pack-years of smoking (trend test: p = 0.003). The proportion of GSTM1 0/0 genotype among patients was 62% compared with 43% among controls (odds ratio = 2.1; 95% CI 1.1-4. 3). The expected interaction between smoking and GSTM1 genotype was not observed.
  
  
  CONCLUSIONS
  This study confirms the findings that a germline homozygous deletion of the GSTM1 gene predisposes to bladder cancer. An interaction with smoking was not found.
authors.affiliation: Department of Urology, University Hospital, Nijmegen, The Netherlands.
authors.forename: N A
authors.initials: NA
authors.lastname: Mungan
authors.forename: K K
authors.initials: KK
authors.lastname: Aben
authors.forename: E
authors.initials: E
authors.lastname: Beeks
authors.forename: E
authors.initials: E
authors.lastname: Kampman
authors.forename: A
authors.initials: A
authors.lastname: Bunschoten
authors.forename: M
authors.initials: M
authors.lastname: Bussemakers
authors.forename: J A
authors.initials: JA
authors.lastname: Witjes
authors.forename: L A
authors.initials: LA
authors.lastname: Kiemeney
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D005854:Germ Cells; D005982:Glutathione Transferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D012907:Smoking / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D005982:Glutathione Transferase