Abstract
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.
Highlights
Bladder cancer is a multi-factorial malignancy influenced by environmental risk factors and molecular variations in metabolism-related genes leading to DNA instability and resulting in the development of cancer [1]
We found that study subjects with the GST Omega 1 (GSTO1) Ala/Ala genotype have a significantly increased bladder cancer (BC) risk (OR = 1.5; 95% confidence interval (CI) = 1.1 2.7)
A statistically significant increased BC risk was found in ever smokers with the GSTO1 Ala/Ala genotype (OR = 4.9; 95% CI = 2.8 - 9.7)
Summary
Bladder cancer is a multi-factorial malignancy influenced by environmental risk factors and molecular variations in metabolism-related genes leading to DNA instability and resulting in the development of cancer [1]. A single nucleotide polymorphism (rs4925) of GSTO1 gene was reported at nucleotide 419 causing an alanine (Ala) to aspartate (Asp) substitution in amino acid 140. This amino acid substitution of GSTO1 may lead to a lower enzyme activity of the variant enzyme in a substrate-specific manner [16]. The GSTO1 Asp/Asp gene genotype caused a substitution in amino acid from hydrophobic to hydrophilic residue and exhibited the thiol-transferase activity only 75% of that of the Ala/Ala genotype [15,16,17]. We tested the joint effect of cigarette smoking and the rs4925 polymorphism of GSTO1 gene on the development of bladder cancer
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