Xeroderma Pigmentosum Complementation Group D (XPD) Codon 751 and Exonuclease 1 Glu 589 Lysgene Polymorphismsare Associated with Hepatocellular Carcinoma in Egyptian Patients with HCV (Genotype-4)

Aim: Xeroderma Pigmentosum Complementation Group D (XPD) is a major DNA repair gene in Nucleotide Excision repair system. Exonuclease 1 (Exo 1) is an important modulator in mismatch repair system. Our aim is to investigate the association of XPD/ERCC2 Lys751Gln (A/C) (rs 13181) and Exo- 1 Glu 589 Lys (G/A) (K589E) polymorphisms with Hepatocellular Carcinoma (HCC) in Egyptian patients. Methods: Fifty HCC patients and 50 healthy controls were included. Genotyping for XPD/ERCC2 Lys751Gln was performed by Real-Time PCR and for Exo- 1 (K589E) Glu/Lys by PCR- RFLP. Results: Patients with XPD Lys751Gln combined (AC + CC) genotypes had an increased risk of HCC compared to the wild AA genotype (p = 0.027, OR = 2.47). The mutant C allele frequency was higher in HCC than in controls, (p = 0.035). Mean serum albumin level was lower in patients carrying (AC + CC) genotypes than in AA genotype (p = 0.027). Median serum levels of ALT, AFP and creatinine were higher in AA genotype than in combined genotypes (p = 0.011, 0.007, 0.045 respectively). Exo- 1 Glu 589 Lys (AA) mutant genotype was associated with increased risk of HCC (p = 0.031).The frequency of the mutant A allele was higher in HCC compared to controls, (p = 0.044). Serum creatinine in wild type was higher than in other genotypes (p = 0.034). Conclusion: XPD Lys751Gln and Exo- 1 Glu589 Lys gene polymorphisms are important HCC modulators in Egyptian patients with HCV genotype 4.