Association of matrix metalloproteinases-9 gene polymorphisms with genetic susceptibility to esophageal squamous cell carcinoma

Matrix metalloproteinases-9 (MMP-9) plays important roles in tumor invasion and metastasis by degrading extracellular matrix components. Variations in the DNA sequence in the MMP-9 gene may lead to altered MMP-9 production and/or activity, and so this may modulate an individual's susceptibility to esophageal squamous cell carcinoma (ESCC). To test this hypothesis, we investigated the association of the MMP-9 polymorphisms and their haplotypes with the risk of ESCC in a Chinese population. There were significant differences in the genotype and allele distribution of P574R polymorphism of the MMP-9 gene among cases and controls. The P574R GG genotypes were associated with a significantly increased risk of ESCC as compared with the CC genotypes (odds ratio OR] = 4.08; 95% confidence interval CI]: 1.58-10.52; p = 0.00). Compared with 279R-574P haplotype, 279R-574R (OR = 3.52; 95% CI: 1.99-6.25) and 279Q-574P (OR = 2.16; 95% CI: 1.07-4.35) haplotypes can increase the onset risk of ESCC statistically, but the role of 279R-574R haplotype is more obvious. MMP-9 P574R polymorphisms and P574R-R279Q haplotype are significantly associated with the risk of ESCC. Our study shows for the first time that MMP-9 gene P574R polymorphism may contribute to a genetic risk factor for ESCC in a Chinese population.