Abstract 4694: Genetic variants of GSTO1, GSTO2, SULT1A1 and ALDH2, environmental exposures and risk of urothelial cancer in Taiwan
Authors: Wang Yuan-Hung , Yeh Shauh-Der , Shen Cheng-Hung , Shen Kun-Hung , Juang Guang-Dar , Chiou Hung-Yi 
Published: February 2011

Introduction: Cigarette smoking, arsenic and occupational exposures are known risk factors of urothelial cancer (UC). Some studies also found that alcohol consumption may be associated with bladder cancer. Phase II enzymes including Glutathione S- transferases (GSTs) or Sulfotransferase (SULT) are responsible to metabolize these environmental carcinogens as well as aldehyde dehydrogenase (ALDH) is an alcohol- metabolized enzyme. To investigate the gene-gene and gene-environment interactions on UC risk, this study included environmental exposures of cigarette smoking, alcohol consumption, arsenic and risk-occupations, and genetic variants of GSTO1, GSTO2, SULT1A1 and ALDH2 in combined analyses.

Materials and Methods: A total of 540 pathologically-confirmed UC cases and 540 cancer-free controls, frequency-matched on age, were recruited from individuals who admitted to the same hospitals with UC cases for a health examination. Genetic variants of these enzymes were determined by PCR-RFLP method. A goodness-of-fit X2 test was performed to examine Hardy-Weinberg Equilibrium (HWE). We used an unconditional multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype analysis was calculated by Haploview 3.2.

Results: Cigarette smoking, arsenic and risk occupational exposures are significantly associated with UC risk. Study subjects with both of cigarette smoking and alcohol consumption have a significantly higher UC risk of 3.0. Significantly increased UC risks of 1.6, 2.5 and 1.8 were found for those carrying GSTO2 A424G-G/G, GSTO2 A-183G -G/G and SULT1A1 G638A-G/G genotypes, respectively. Individuals with risk diplotypes of GSTO1/2 also have a significantly higher UC risk of 1.8. Those carrying one or more risk genotypes/diplotypes of these enzymes have a significantly increased UC risk (OR=2.3). Subjects with cigarette smoking/alcohol consumption and occupational exposures (≥1), arsenic exposure (high), and risk genotypes/ diplotypes of these enzymes (≥1) have a significantly increased UC risk of 6.8.

Conclusion: In addition to significant effects from exposures of environmental risk factors and risk genotypes/diplotypes of these enzymes on UC risk, the effects on the development of UC will be more predominant especially under the existence of gene-environment interactions. Therefore, a larger sample size and other functional polymorphisms of candidate genes should be took into consideration to provide a more comprehensive understanding of UC.

Keywords: Glutathione S- transferases; Sulfotransferase; Aldehyde dehydrogenase; Urothelial cancer

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4694.