Gene polymorphisms of glutathione S-transferase omega 1 and 2, urinary arsenic methylation profile and urothelial carcinoma.

Abstract

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.

• Authors: Chi-Jung Chung, Yeong-Shiau Pu, Chien-Tien Su, Chao-Yuan Huang, Yu-Mei Hsueh
• Journal: The Science of the total environment (Sci Total Environ) Vol. 409 Issue 3 Pg. 465-70 (Jan 01 2011) ISSN: 1879-1026 [Electronic] Netherlands
• PMID: 21094982 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Chemical References

• Arsenicals
• Environmental Pollutants
• GSTO1 protein, human
• GSTO2 protein, human
• Glutathione Transferase
• monomethylarsonic acid
• Arsenic

Topics

• Arsenic (urine)
• Arsenicals (metabolism)
• Carcinoma (epidemiology, genetics, metabolism)
• Environmental Pollutants (urine)
• Female
• Genetic Predisposition to Disease
• Glutathione Transferase (genetics, metabolism)
• Humans
• Male
• Methylation
• Middle Aged
• Polymorphism, Single Nucleotide
• Risk Assessment
• Urologic Neoplasms (epidemiology, genetics, metabolism)
• Urothelium (metabolism, pathology)