MMP2 gene polymorphism and tumor susceptibility study

Abstract

Abstract Background：Genetic polymorphisms in the signaling axis of metalloproteinases (MMPs) can influence cancer susceptibility. The relationship between two MMPs gene variants, rs243865 C/T and rs2285053 C/T, and cancer risk still needs to be explored. The aim of this study was to comprehensively investigate the relationship between MMPs polymorphisms and cancer susceptibility. Methods: We conducted a comprehensive assessment using odds ratios (ORs), corresponding 95% confidence intervals (CIs), and in silico tools to evaluate the effect of MMP2 variations. Immunohistochemical staining (IHS) and GSEA analysis were used to investigate the expression of MMP2 in urinary system cancer. Results: The pooled analysis involved 86 case-control studies including 26326 cancer patients and 32651 controls. The rs243865 C/T polymorphism was associated with the risk of cancer (C-allele versus T-allele, OR = 0.836, 95%CI = 0.730-0.958, P = 0.010; TC versus CC, OR =0.781, 95%CI = 0.686-0.890, P = 0.000; TT+TC versus CC, OR = 0.798, 95%CI = 0.693-0.919, P = 0.002), especially for cancers of the prostate, ENT, lung, gastric, esophageal, head and neck. Variation rs2285053 C/T was associated with cancer susceptibility, especially for lung and gastric cancer. IHS analysis showed that MMP2 was upregulated in bladder cancer. GSEA revealed that the Leukocyte transendothelial migration pathway, focal adhesion pathway, and JSK-STAT-signaling pathway were enriched in the high MMP2 expression group. Conclusions: The MMP2 rs243865 C/T polymorphism may be associated with susceptibility of prostate cancer.