MMP-9 Genotypes Serve as Oral Cancer Predictive Marker for Smokers

Background/Aim: Oral cancer represents a major health burden in Taiwan, with tobacco use, alcohol consumption, and betel quid chewing recognized as predominant environmental risk factors. Matrix metalloproteinase-9 (MMP-9) has been implicated in tumor invasion and progression, and the promoter polymorphism rs3918242 has been investigated as a potential genetic determinant of cancer susceptibility. The study aims to reveal the contribution of MMP-9 genotypes to oral cancer susceptibility.

Materials and Methods: In this case-control study, 958 Taiwanese patients with histologically confirmed oral cancer and 958 cancer-free controls were genotyped for MMP-9 rs3918242 using PCR-RFLP. The association was evaluated via chi-square with Yates’ correction in addition to odds ratio (OR) and corresponding 95% confidence interval (CI).

Results: The control group exhibited genotype frequencies consistent with the Hardy-Weinberg equilibrium (p=0.3192). Overall, no statistically significant association was observed between MMP-9 genotypes heterozygous CT (OR=1.09, 95%CI=0.89-1.36, p=0.4128) or homozygous TT (OR=1.65, 95%CI=0.96-2.84, p=0.0910) and oral cancer risk. Recessive and dominant genetic models similarly revealed no significant associations (OR=1.61 and 1.15, 95% CI=0.94-2.77 and 0.94-1.41, p=0.1066 and 0.1968). Allelic analysis also indicated no significant effect of the T allele on oral cancer susceptibility (OR=1.17, 95%CI=0.98-1.40, p=0.0843). Stratification by sex yielded non-significant associations in both males and females. Importantly, a gene-environment interaction analysis revealed that smokers carrying the TT genotype exhibited a significantly elevated risk of oral cancer (adjusted OR=1.91, 95% CI=1.04-3.88), whereas no interaction was observed with alcohol consumption or betel quid chewing.

Conclusion: These findings suggest that while MMP-9 rs3918242 variants alone do not serve as reliable predictive biomarkers for oral cancer in Taiwanese, the TT genotype may synergize with cigarette smoking to increase susceptibility. Future studies in ethnically diverse populations, coupled with mechanistic investigations of MMP-9 expression in response to tobacco exposure, are warranted to elucidate the functional impact of this polymorphism in oral carcinogenesis.