Impact of matrix metalloproteinase-11 gene polymorphisms upon the development and progression of hepatocellular carcinoma

Bin Wang, Chin-Jung Hsu, Hsiang-Lin Lee, Chia-Hsuan Chou, Chen-Ming Su, Shun-Fa Yang, Chih-Hsin Tang, Bin Wang, Chin-Jung Hsu, Hsiang-Lin Lee, Chia-Hsuan Chou, Chen-Ming Su, Shun-Fa Yang, Chih-Hsin Tang

Abstract

Hepatocellular carcinoma (HCC) is a liver malignancy and a major cause of cancer mortality worldwide. Matrix metalloproteinase-11 (MMP-11), also known as stromelysin-3, plays a critical role during tumor migration, invasion and metastasis. Here, we report on the association between five single nucleotide polymorphisms (SNPs) - rs738791, rs2267029, rs738792, rs28382575, and rs131451 - of the MMP-11 gene and HCC susceptibility, as well as clinical outcomes, in 293 patients with HCC and in 586 cancer-free controls. We found that carriers of the CT+TT allele of the rs738791 variant were at greater risk of HCC compared with wild-type (CC) carriers. Moreover, carriers of at least one C allele (C/T+C/C genotype) at the MMP-11 SNP rs738792 were likely to progress to Child-Pugh B or C grade, while individuals with at least one C allele (C/T+C/C genotype) at the MMP-11 SNP rs28382575 were at higher risk of developing stage III/IV disease, large tumors or lymph node metastasis. We believe that genetic variations in the MMP-11 gene may help to predict early-stage HCC and act as reliable biomarkers for HCC progression.

Keywords: Hepatocellular carcinoma; MMP-11 polymorphisms; Single nucleotide polymorphism; Susceptibility.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
MMP-11 displays a significant eQTL association with the rs738792 genotype in liver tissue (GTEx data set).

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