Meta-Analysis of MMP2, MMP3, and MMP9 Promoter Polymorphisms and Head and Neck Cancer Risk

BACKGROUND: The 1306 C>T, 1171 5A>6A, and 1562C>T polymorphisms of matrix metalloproteinase (MMP) 2, MMP3, and MMP9 genes, respectively, have been found to be functional and may contribute to head and neck carcinogenesis. However, the results of case-control studies examining associations between MMP polymorphisms and head and neck cancer (HNC) risk remain inconclusive. Therefore, we performed a meta-analysis to further evaluate the role of these polymorphisms in HNC development. METHODS: We searched PubMed, ISI Web of Knowledge, MEDLINE, Embase, and Google Scholar to identify all published case-control studies of MMP2-1306 C>T, MMP3-1171 5A>6A, and MMP9-1562 C>T polymorphisms and HNC risk in the meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between these polymorphisms and HNC risk. RESULTS: Thirteen studies were included in this meta-analysis. For MMP2-1306 C>T polymorphism, significant associations were observed under three genetic models both in overall comparison and in a hospital-based subgroup, and in oral cavity cancer and nasopharyngeal cancer under dominant model as well. For MMP3-1171 5A>6A and MMP9-1562 C>T polymorphisms, no association was found in overall comparison; however, in subgroup analyses based on ethnicity and tumor site, significant associations were detected between the MMP3-1171 5A>6A polymorphism and HNC risk in a European population and pharyngeal/laryngeal cancer under two genetic contrasts. CONCLUSION: This meta-analysis suggests that the MMP2-1306 C>T polymorphism is associated with HNC risk, as is the MMP3-1171 5A>6A polymorphism specifically in some subgroups. Further studies with larger sample sizes are warranted.