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Matrix Metalloproteinase 1, 3, and 9 Polymorphisms and Esophageal Squamous Cell Carcinoma Risk

Xuan Guan, Xiang Wang, Hao Luo, Jing Wu, Xiao Zhang, Jin Wu

School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, China (mainland)

Med Sci Monit 2014; 20:2269-2274

DOI: 10.12659/MSM.892413

Available online:

Published: 2014-11-13

Background: Matrix metalloproteinases (MMPs) are multifunctional zinc-dependent proteinases that play a fundamental role in the pathogenesis of tumors. We have analyzed the association between 3 single-nucleotide polymorphisms (SNPs; MMP1 −1607 1G/2G, MMP3 −1612 5A/6A, and MMP9 −1562 C/T) and the risk of esophageal squamous cell carcinoma (ESCC).
Material and Methods: We investigated these 3 SNPs in 132 patients and 132 controls using polymerase chain reaction-restriction fragment length polymorphism methods. The MMP1 and MMP3 genes are located on the same chromosome. Haplotype analysis was performed to study the combined effect of the linked MMP polymorphisms on ESCC risk.
Results: The MMP1 and MMP9 promoter polymorphisms were not associated with ESCC risk, while the MMP3 −1612 5A/6A polymorphism was significantly associated with susceptibility to ESCC. Patients carrying the 5A allele had a significantly higher risk for developing ESCC compared with individuals carrying the 6A allele (OR=1.93; 95% CI 1.34–2.77; p<0.01). The 2G-5A and 1G-5A haplotypes were associated with a significantly increased risk of ESCC as compared with the 2G-6A haplotype (OR=2.04, 95% CI 1.37–3.04 and OR=3.65, 95% CI 1.26–10.55, respectively).
Conclusions: These findings implicate this MMP3 polymorphism as a contributor to ESCC susceptibility.

Keywords: Case-Control Studies, Carcinoma, Squamous Cell - genetics, Esophageal Neoplasms - genetics, Gene Frequency - genetics, Genetic Predisposition to Disease, Haplotypes - genetics, Matrix Metalloproteinase 1 - genetics, Matrix Metalloproteinase 3 - genetics, Matrix Metalloproteinase 9 - genetics, Polymorphism, Single Nucleotide - genetics, Risk Factors