Possible Relationship between Matrix Metalloproteinases Genotyping and Risk of Hepatocellular Carcinoma in HCV Infected Patients

Abstract

Background: The annual number of new cases of hepatocellular carcinoma (HCC) worldwide is over 1 million. In developing countries, the major cause of HCC is chronic hepatitis C virus (HCV) infection. Various studies have reported an association between functional gene polymorphism of matrix metalloproteinases (MMP) promoters and different cancers. Rationale: This study examined the association between MMP1 -1607, MMP9-1562, MMP14-6727 and MMP14-6767 gene polymorphisms and risk of HCC in HCV infected patients.   Methods: The study enrolled 160 HCC patients, 91 with & 69 without chronic HCV infection, and 140 healthy subjects as control group. Genomic DNA was analysed for MMPs gene polymorphism using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) for MMP1 and MMP9 but real time PCR was used for MMP14 genotyping. Results: MMP1-2G allele carriers had higher susceptibility of developing HCC in HCV infected patients. MMP9-1562 T/T genotype had high risk of developing HCC in HCV and non HCV related patients when compared to healthy controls. A significant lower risk for HCC was shown in individuals with MMP14-6767 G/A. The distribution frequency of MMP14-6767 G and MMP14-6727 C allele and homozygote genotype was significantly higher in HCC patients. Conclusion: MMP-1 -1607 2G allele carriers would alter the risk of HCC under specific conditions such as chronic infection with HCV. People with MMP9-1562 T/T genotype are at risk of developing HCC. MMP14-6767 G and MMP14-6727 C allele carriers and homozygote genotype might contribute to the prediction of susceptibility and pathological development of HCC in HCV infected patients.