Association between human glutathione S-transferase omega rs4925 polymorphism and bladder cancer

Glutathione S-transferases (GSTs) play an important role in the detoxification of polycyclic aromatic hydrocarbons and aromatic amines, the toxic substances contained in cigarettes. GST Omega 1 (GSTO1) not only utilizes glutathione in conjugation reaction but also contributes to the biotransformation of several xenobiotics. A single nucleotide polymorphism (Ala-140Asp) of GSTO1 gene causing variations in enzyme activity may influence individual susceptibility to bladder cancer (BC). It is hypothesized that genetic polymorphism of GSTO1 gene has an effect on BC risk in particular by interacting with cigarette smoking. A total of histopathologically confirmed 300 BC patients and 300 cancer-free controls were recruited from February 2002 to February 2009. Genotyping of the GSTO1 Ala140Asp polymorphism was determined using a polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) method. The odds ratio (OR) and 95% confidence interval (CI) were calculated as a measure of the combined effect of cigarette smoking and the GSTO1 Ala140Asp polymorphism on BC risk. We found that study subjects with the GSTO1 Ala/Ala genotype have a significantly increased BC risk (OR = 1.5;95% CI = 1.1 - 2.7). A statistically significant increased BC risk was also found in ever smokers with the GSTO1 Ala/Ala genotype (OR = 4.9;95%CI = 2.8 - 9.7). In conclusion, this study provides an epidemiologic evidence of a significantly increased BC risk among ever smokers with the GSTO1 Ala/Ala genotype.

<i>Survivin</i>promoter rs9904341 polymorphism is associated with tumor stage and grade in patients with bladder cancer

Survivin is an inhibitor of apoptosis protein and also plays a important role in the development of several malignancies. To investigate the association between survivin promoter –31 G/C (rs9904341) polymorphism and bladder cancer (BC) risk. A total of 200 pathologically confirmed BC cases and 200 unrelated cancer-free controls were recruited in Chiayi Christian Hospital from August 2002 to May 2009. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the –31 G/C polymorphism at survivin promoter region. There was a significant difference in the frequency distribution of survivin promoter –31 G/C polymorphism in BC cases as compared to controls. Among BC cases, individuals with the C/C genotype of survivin promoter have a significantly higher prevalence of invasive (T2-T4) or high-grade (G2-G3) tumors as compared to those who carried the G/G genotype. In conclusion, our findings suggest that the survivin promoter –31 G/C polymorphism was not only associated with clinical stage and pathological grade but also involved in the development of bladder cancer.