Epidemiological Evidence Between Variants in Matrix Metalloproteinases-2, -7, and -9 and Cancer Risk

BACKGROUND: Matrix metalloproteinases (MMPs), a kind of proteases, have a critical function in cancer occurrence, invasion, and migration. MMP gene variants (e.g., MMP-2, MMP-7, and MMP-9) can affect the biological functions of these enzymes and lead to the occurrence and progression of cancer, which has become a hot topic in recent years, but the corresponding results are still controversial. In this context, here, the meta-analysis was conducted for assessing the relations of variants in MMP-2, MMP-7, and MMP-9 with the risk of various cancers. METHODS: PubMed, Web of Science, and Medline were systemically searched, and data were extracted from all eligible studies so as to investigate the susceptibility of MMP-2, MMP-7, and MMP-9 to different types of cancers. The association between a variant in MMP and cancer susceptibility was analyzed through odds ratios (ORs) as well as 95% CIs. The Venice criteria and false-positive report probability (FPRP) were adopted to evaluate epidemiological evidence of significant associations discovered. RESULTS: The associations between the variants of MMPs and cancer risk in 36,530 cases and 41,258 controls were found, with 12 associations (MMP-2 rs243865 with esophageal cancer and lung cancer, MMP-7 rs11568818 with bladder and cervical cancer, and MMP-9 rs3918242 with breast cancer) rated as strong associations for cancer risk and 7 and 15 as moderate and weak associations, respectively. These significant associations were mostly found in Asians. CONCLUSIONS: These findings support the relations between variants of MMP-2, MMP-7, and MMP-9 and various cancers risk, demonstrating the credibility of these relations.