Systematic evaluation of genetic polymorphisms in carcinogen metabolizing enzymes associated with the risk of oral potentially malignant disorders occurrence.

BACKGROUND/PURPOSE: Accumulated studies investigate the association of single-nucleotide polymorphisms (SNPs) in carcinogen metabolizing enzymes with oral potentially malignant disorders (OPMD) risk. However, these results were inconsistent and conflicting. The purpose of this pooled analysis was to systematically evaluate the associations of SNPs in 6 enzymes (CYP1A1, CYP2E1, GSTM1, GSTM3, GSTT1 and GSTP1) with risk of OPMD occurrence.

MATERIALS AND

METHODS

A systematic evaluation was performed to identify all eligible case ndash;control studies on the association between SNPs in 6 enzymes and OPMD onset. Odds ratios (ORs) and 95 % confidence intervals (CIs) were pooled to estimate association strength.

RESULTS

A significant association of CYP2E1 PstI polymorphism with OPMD was found (OR, 1.46; 95%CI, 1.07-2.00) in 430 cases and 818 health controls. A significant association of GSTM1 null genotype with OPMD, especially oral leukoplakia, was found (OR, 1.72; 95%CI, 1.24-2.37) in 2228 cases and 4425 controls. A significant association of GSTT1 null genotype with OPMD, particularly oral submucous fibrosis, was found (OR, 1.50; 95%CI, 1.01-2.22) in 1798 cases and 3934 controls. A marginally significant association of GSTM3 polymorphism with OPMD was found (OR, 1.41; 95%CI, 1.00-1.98) in 321 cases and 622 controls. There was no significant association of polymorphisms in CYP1A1, CYP2E1 RsaI variant, and GSTP1 with OPMD.

CONCLUSION

This analysis for the first time investigated SNPs in carcinogen metabolizing enzymes with OPMD, suggesting that polymorphisms in CYP2E1 PstI, GSTM1, GSTM3 and GSTT1 play roles in OPMD occurrence and highlighting their potential in risk stratification and early detection strategies.