A germline homozygote deletion of the glutathione-S-transferase Mu1 gene predisposes to bladder cancer

introduction and Objectives: Numerous studies have shown smoking and specif ic occupational exposures to be risk factors for bladder cancer. The risk o f bladder cancer may be modified by the activity of carcinogen metabolizing enzymes. The glutathione-S-transferase Mu1 enzyme (GSTM1) detoxifies aryle poxides which are formed after exposure to certain polycyclic aromatic hydr ocarbons and possibly aromatic amines. Approximately 40% of Caucasians lack GSTM1 activity due to a homozygous deletion of the GSTM1 locus on chromoso me 1p13 (GSTM1 0/0 genotype). The a im of th is study was to evaluate the c ombined effect of smoking and GSTM1 genotype on the risk of bladder cancer. Materials and 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 standardi zed questionnaire. DNA was extracted from white blood cells. The GSTM1 geno type was determined by a PCR-based method. Resuits: 92% of the 61 patients had a history of smoking compared with 81% of the controls. There was a sig nificant dose-response relationship for pack-years of smoking (trend test: p = 0.003). The proportion of GSTM1 0/0 genotype among patients was 62% com pared with 43% among controls (odds ratio = 2.1; 95% CI 1.1-4.3). The expec ted interaction between smoking and GSTM1 genotype was not observed. Conclu sions: This study con firms the findings that a germline homozygous deletio n of the GSTM1 gene predisposes to bladder cancer. An interaction with smok ing was not found. Copyright (C) 2000 S. Karger AG, Basel.