Quantitative analysis of the association between sulfotransferase isoform 1A1 polymorphism and risk of urothelial carcinoma

Abstract

Sulfotransferase isoform 1A1 (SULT1A1) is a member of the sulfotransferase family that plays an important role in the biotransformation of numerous carcinogenic and mutagenic compounds through sulfation. A number of case-control studies were conducted to investigate the association between the Arg213His polymorphism in SULT1A1 and the risk of urothelial carcinoma (UC) in humans. However, the results were inconsistent. A meta-analysis based on 10 case-control studies was performed to address this issue. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of this association. Between-study heterogeneity was assessed with the Chi-square-based Q test. Overall, a possibly decreased risk of UC was associated with the SULT1A1 A/A polymorphism for the heterozygote model (OR=0.86, 95% CI: 0.76-0.98, P=0.471). In the subgroup analysis by cancer type, the results indicated that individuals with the G/G genotype had a significantly higher bladder cancer (BC) risk (GA vs. GG: OR=0.88, 95% CI: 0.74-0.99, P=0.626; GA/AA vs. GG: OR=0.85, 95% CI: 0.74-0.97, P=0.504), which was contrary to the results of the upper urinary tract urothelial carcinoma (UTUC) group (AA vs. GG: OR=2.18, 95% CI: 1.28-3.69; AA vs.GA/GG: OR=2.05, 95% CI: 1.24-3.38). In addition, stratification by smoking status demonstrated that the Arg213His polymorphism was associated with a decreased risk of UC in non-smokers (OR=0.70, 95% CI: 0.53-0.92) but not in smokers (OR=0.85, 95% CI: 0.70-1.03) under the dominant model. In conclusion, this meta-analysis demonstrated a significant association between the SULT1A1 Arg213His polymorphism and BC. However, there was insufficient evidence to support a consistent association between this polymorphism and UC, partly due to the differences between BC and UTUC.