Matrix metalloproteinase-9 gene polymorphism in hepatocellular carcinoma patients with hepatitis B and C viruses

Abstract

ABSTRACT. Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. In Egypt, the incidence of HCC has doubled over the last decade. Matrix metalloproteinase-9 (MMP-9) plays a key role in cancer invasion and metastasis by degrading the extracellular matrix and basement membrane barriers. A cytosine (C)/ thymidine (T) single nucleotide polymorphism at position -1562 in the MMP-9 promoter is reported to influence the expression of the MMP-9 gene. The association between MMP-9 gene polymorphisms and HCC patients with hepatitis C and B viruses (HCV and HBV) was examined in 91 patients with HCC and viral hepatitis (55 HCV and 36 HBV). The results were compared with those of 42 HCC patients without viral hepatitis and 60 healthy individuals with no liver infection. Polymorphisms of the MMP-9 gene were investigated by polymerase chain reaction amplification followed by restriction fragment length polymorphism analysis. The serum MMP-9 level was quantitatively determined using a human MMP-9 enzyme-linked immunosorbent assay, which showed that homozygosity of the MMP-9 promoter (TT) was more frequent in patients with HCC and chronic HCV or HBV infection when compared with the control group (49.1, 52.8, and 35.7%, respectively). In addition, we observed significant elevation of serum MMP-9 levels in all HCC groups compared to controls. It was concluded that patients with the MMP-9 TT genotype are at risk of developing HCC and HBV or HCV. People with significantly elevated serum levels of MMP-9 are at risk of developing HCC.

Association and Prognostic Significance of the Functional −1562C/T Polymorphism in the Promoter Region of MMP-9 in Turkish Patients with Gastric Cancer

“…For example, this common genetic variant has been associated with an increased risk of prostate cancer [21], breast cancer [22], and hepatocellular carcinoma [23]. However, the results of our study did not point toward a major role of the MMP-9 −1562C/T polymorphism in the pathogenesis and clinical course of GC in Turkish subjects.…”

A Review of Cancer Genetics and Genomics Studies in Africa

“…The last group of genes that have been studied on hepatocellular carcinoma in Africa are those involved in angiogenesis, including VEGF , MMP , RASSF1A , and RECK . In Egypt, Samamoudy et al ( 230 ) reported that patients with MMP9 (rs3918242) are at high risk of developing liver cancer while RECK (rs12814325) ( 231 ) could account for the disease progression and metastasis.…”

Protein phosphatase 2A regulation of markers of extracellular matrix remodelling in hepatocellular carcinoma cells: functional consequences for tumour invasion

“…A recognized hallmark of invasion is the proteolytic breakdown of the extracellular matrix (ECM) through dysregulation of the matrix metalloproteinase system (Hanahan and Weinberg, ; Bonnans et al, ). In addition to MMP‐9 (El Samanoudy et al, ), MMP‐2, MMP‐13, TIMP‐1 and TIMP‐3 are also involved (Altadill et al, ; Gu et al, ). Interestingly, their effects are not limited to degradation of the ECM.…”