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This in turn downregulates the tumor suppressor RASSF1, inhibiting apoptosis and leading to HCC development, indicating a negative impact of CTLA4 gene polymorphism on HCV-mediated HCC cases. A major determinant of disease progression could be immune system genetic variants, together with the presence of costimulatory factors. The rs2073498 and rs7574865 variations in the RASSF1A and STAT4 genes, respectively, could be genetic susceptibility factors for Egyptian patients with HCV-mediated HCC.A national surveillance system on hand, foot