Role of MMP14 gene polymorphisms in susceptibility and pathological development to hepatocellular carcinoma

Ann Surg Oncol. 2011 Aug;18(8):2348-56. doi: 10.1245/s10434-011-1574-x. Epub 2011 Feb 5.

Abstract

Background: Early detection of hepatocellular carcinoma (HCC) is seldom available because of the lack of reliable markers. Matrix metalloproteinase (MMP) 14 is a cell surface proteinase that displays a broad spectrum of activity against extracellular matrix components and promotes the invasion/metastasis of cells. MMP14 is overexpressed in HCC, and the level is correlated with poor overall survival. The purpose of this study was to examine whether the MMP14 gene polymorphisms are associated with the susceptibility and clinicopathological development of HCC.

Methods: A total of 135 patients with HCC and 496 healthy control subjects were recruited. Six single nucleotide polymorphisms (SNPs) of MMP14 genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping and haplotype-base analysis.

Results: A significant (p < 0.05) lower risk for HCC was shown in the individuals with MMP14 +6767 G/A and +7096 C/C genotypes compared with those with corresponding wild-type homozygotes; high frequency for anti-hepatitis C virus and cirrhosis positive were shown in the HCC patients with MMP14 +7096 TC/CC genotype after adjusting for other confounding factors. The distribution frequency of -165 T: +221 T: +6727 C: +6767 G: +7096 T: +8153 G haplotype and diplotype was significantly higher in the HCC patients than healthy control subjects.

Conclusions: The +6767 and +7096 polymorphic genotypes and haplotype -165 T: +221 T: +6727 C: +6767 G: +7096 T: +8153 G of MMP14 gene might contribute to the prediction of susceptibility and pathological development to HCC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / secondary
  • Case-Control Studies
  • DNA, Neoplasm / genetics
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 14 / genetics*
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide / genetics*
  • Real-Time Polymerase Chain Reaction
  • Survival Rate
  • Treatment Outcome

Substances

  • DNA, Neoplasm
  • MMP14 protein, human
  • Matrix Metalloproteinase 14