Promoter polymorphisms of MMP 1 and 2 genes and risk for hepatocellular carcinoma: Case-control analysis in Turkish patients

Abstract

Purpose: Matrix metalloproteinases are established as strong prognostic markers for hepatocellular carcinoma which is one of the most progressive and aggressive cancer types worldwide. Hepatocellular carcinoma is very common in various populations, but the pathogenetic link between MMPs is limited so far. Due to asociation with invasion in cancer metastasis, the matrix metalloproteinases MMP-1 and MMP-2 are candidate genes for predisposition to hepatocellular carcinoma.

Patients and Methods: A total of 73 patients who were diagnosed as having hepatocellular carcinoma and had undergone liver transplantation were enrolled in the study. Following DNA extraction polymerase chain reaction-restriction fragment lenght polymorphism molecular genetic analyses were performed. By case-control and genotype-phenotype correlation analysis, we investigated the risk of association of MMP-1 and MMP-2 promoter polymorphisms in 73 Turkish hepatocellular carcinoma patients compared to healthy controls.

Results: Genotypic distributions of the MMP2 -735 C/T and MMP1 -1607 1G/2G polymorphisms were in Hardy-Weinberg equilibrium in patient and control groups (p>0.05). In case-control analyses, the distribution of the genotypes and allele frequencies in the cases did not differ from those in the control group (p>0.05). In genotype-phenotype correlation analysis; for MMP1 -1607 1G/2G polymorphism 2G/2G genotype was associated with portal vein invasion (p<0.02). With regard to the post-transplantation results of the present study the 4-year survival rate in the patients was 77,3% and the recurrencefree survival rate in the post-transplant phase was 96,2%.

Conclusion: No significant association was determined between Turkish hepatocellular carcinoma prognosis and post-transplantation metastasis and invasion with MMP2 -735 C/T and MMP1 -1607 1G/2G polymorphisms as risk predictors.