Systematic evaluation of genetic polymorphisms in carcinogen metabolizing enzymes associated with oral potentially malignant disorders progression to oral cancer risk.

BACKGROUND/PURPOSE: Increasing studies investigate the association of polymorphisms in carcinogen-metabolizing enzymes with oral potentially malignant disorder (OPMD) progression to oral squamous cell carcinoma (OSCC) risk. However, these results remain inconsistent and conflicting. This pooled analysis aimed to systematically evaluate the 5 enzymes (CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1) polymorphisms in OPMD versus OSCC. MATERIALS AND METHODS: A systematic literature search was conducted to identify all eligible case-control studies on the association between SNPs in the 5 enzymes in OPMD versus OSCC. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to access association strength. RESULTS: No significant association of CYP1A1 MspI polymorphism (OR, 1.38; 95%CI, 0.80-2.38) in OPMD with OSCC risk was observed based on 5 eligible studies involving 624 cases of OPMD and 1529 OSCC. As for GST genes, an increased risk of GSTM1 null genotype (OR, 1.72; 95%CI, 1.24-2.37) with OPMD, especially oral leukoplakia, progression to OSCC was found based on 11 eligible studies involving 1195 OPMD patients and 2219 OSCC controls. However, there was no significant association of GSTT1, GSTM3 or GSTP1 polymorphisms in OPMD with OSCC risk. CONCLUSION: This is the first pooled analysis on polymorphisms in carcinogen-metabolizing enzymes in OPMD versus OSCC. The results suggested that the GSTM1 null genotype was a significant genetic risk factor for OPMD progression to OSCC, highlighting its potential for improving risk stratification and early detection, particularly for oral leukoplakia.