Cancer Genetics and Cytogenetics 125 (2001) 1–4 0165-4608/01/$ – see front matter © 2001 Elsevier Science Inc. All rights reserved. PII: S0165-4608(00)00307-1 Lead article Glutathione S-transferase M1 gene polymorphism in bladder cancer patients: a marker for invasive bladder cancer? Dilek Aktas a, *, Haluk Ozen b , Necmettin Atsu b , Ali Tekin b , Sinan Sozen b , Ergul Tuncbilek a a Department of Genetics, Hacettepe University School of Medicine, 06100, Sihhiye, Ankara, Turkey b Department of Urology, Hacettepe University School of Medicine, 06100, Sihhiye, Ankara, Turkey Received 17 April 2000; received in revised form 7 June 2000; accepted 21 June 2000 Abstract The glutathione S-transferase M1 (GSTM1) gene is polymorphic in humans, and the deficiency in enzyme activity of GSTM1 is caused by the inherited homozygous absence of the GSTM1 gene, or the “null” genotype (GSTM1, 0/0). The increased risk of bladder cancer has been shown to corre- spond with this gene defect. No reports, however, have been found in the literature regarding GSTM1 gene deficiency with superficial and invasive bladder cancer. In this study, we examined the association of the GSTM1-null genotype with superficial and invasive bladder cancer. Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the GSTM1 gene defect in Turkish patients with superficial bladder cancer (N = 61), invasive bladder cancer (N = 42), and control subjects (N = 202) who had no history of cancer. The GSTM1 null genotype was observed in 34.7% of the control subjects and in 54.3% of total bladder cancer patients (OR: 2.246; 95% CI: 1.384–3.645, P: 0.00094). In other words, the presence of the GSTM1-null genotype significantly increased the risk of bladder cancer development. Among invasive bladder cancers, the frequency of the GSTM1-null genotype was 64.3% (OR: 0.294, 95% CI: 0.147–0.590, P: 0.0003). This was also significantly higher than control subjects, indicating that patients carrying this genotype were at increased risk for developing invasive bladder cancer. This relationship was not statistically significant in the superficial bladder cancer group (OR: 0.585, 95% CI: 0.327– 1.045, P: 0.06). Our results indicate that GSTM1 gene polymorphism should be considered as an important risk modifier in the development of bladder cancer and might be used as a predictive marker for invasive bladder cancer. © 2001 Elsevier Science Inc. All rights reserved. 1. Introduction Bladder cancer is the second most common cancer of the genitourinary tract; the average age at the time of diagnosis is 65 years [1]. Epidemiological studies have shown that the risk of bladder cancer development is associated with car- cinogen exposure and cigarette smoking [2–4]. Glutathione (GSH) and GSH-dependent enzymes are in- volved in the cellular metabolism and detoxification of car- cinogenic products; the GSH-S-transferase (GST) is of criti- cal importance in these reactions. GST catalyzes reactions between GSH and a variety of electrophilic compounds to form S-substituted GSH conjugate [5,6]. The glutathione S-transferase M1 (GSTM1) gene belongs to the GST gene family, and it catalyzes the detoxification of polycyclic aro- matic hydrocarbons (PAH), which consist of many well- recognized mutagenic or carcinogenic agents. GSTM1 plays a protective role against the development of cancer. The de- ficiency of this enzyme activity is caused by the inherited homozygous absence of the GSTM1 gene, the “null” geno- type (GSTM1, 0/0) [7]. Previous studies have indicated that GSTM1-null genotype is associated with increased risk for tobacco-related cancer due to a decreased ability to detoxify PAH [8–10]. Several researchers have aimed to determine the GSTM1 genotype in patients with bladder cancer in different ethnic groups [2,7,11,12]. In the present study, we investigate the frequency of homozygous absence of the GSTM1 gene and the importance of this polymorphism as a risk factor among Turkish bladder cancer patients. We have also analyzed our results in regard to the stage and grade of the tumor. * Corresponding author. E-mail address: dilekaktas6@hotmail.com (D. Aktas).