Genetic polymorphisms in
arsenic-metabolizing
enzymes may be involved in the biotransformation of inorganic
arsenic and may increase the risk of developing urothelial
carcinoma (UC). The present study evaluated the roles of
glutathione S-transferase omega 1 (GSTO1) and GSTO2 polymorphisms in UC
carcinogenesis. A hospital-based case-control study was conducted. Questionnaire information and
biological specimens were collected from 149 UC cases and 251 healthy controls in a non-obvious inorganic
arsenic exposure area in Taipei, Taiwan. The urinary
arsenic profile was determined using high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Genotyping for GSTO1 Ala140Asp and GSTO2 Asn142Asp was conducted using polymerase chain reaction-restriction fragment length polymerase. GSTO1 Glu208Lys genotyping was performed using high-throughput matrix-assisted
laser desorption and ionization time-of-flight mass spectrometry. A significant positive association was found between total
arsenic, inorganic
arsenic percentage and
monomethylarsonic acid percentage and UC, while
dimethylarsinic acid percentage was significantly inversely associated with UC. The minor allele frequency of GSTO1 Ala140Asp, GSTO1 Glu208Lys and GSTO2 Asn142Asp was 18%, 1% and 26%, respectively. A significantly higher MMA% was found in people who carried the wild type of GSTO1 140
Ala/Ala compared to those who carried the GSTO1 140
Ala/Asp and
Asp/Asp genotype (p=0.02). The homogenous variant genotype of GSTO2 142
Asp/Asp was inversely associated with UC risk (OR=0.17; 95% CI, 0.03 - 0.88; p=0.03). Large-scale studies will be required to verify the association between the single nucleotide polymorphisms of
arsenic-metabolism-related
enzymes and UC risk.