Polymorphisms of DNA repair genes in Korean hepatocellular carcinoma patients with chronic hepatitis B: possible implications on survival.
OBJECTIVE
We aimed at determining whether single nucleotide polymorphisms (SNPs) of DNA repair genes influence the development and clinical outcomes of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).


METHODS
We evaluated 14 SNPs of eight DNA repair genes in 708 patients with HCC and 388 HBsAg positive controls without HCC. The Kaplan-Meier methods with log-rank test and Cox regression models were used to compare survival of HCC patients according to the genotype.


RESULTS
The SNP of XRCC4 rs1805377 was significantly associated with decreased risk of HCC development (OR, 0.592; p=0.028) and improved overall survival of patients with HCC (median survival time (MST) of 48, 72, and 89 months for the AA, AG, and GG genotypes, respectively; p=0.044). In addition, SNP of OGG1 rs1053133 was significantly associated with postoperative recurrence (OR, 0.604; p=0.049), tumor differentiation (OR, 0.571; p=0.041), and improved survival of resected HCC (MST of 55 and 108 months for the GG and GC/CC genotypes, p=0.001). The multivariate analysis showed that OGG1 rs1052133, XRCC1 rs25487, ERCC5 rs2018836, ERCC5 rs3818356, and XRCC4 rs1805377 had a significant effect on survival. Moreover, a strong dose-dependent association was observed between the number of putative high-risk genotypes of OGG1, XRCC1, ERCC5, and XRCC4 with the overall survival. The MST of HCC with ≥2 putative high-risk genotypes was significantly prolonged compared to those with ≥3 high-risk genotypes (76 vs. 46 months, respectively, p=0.002).


CONCLUSIONS
Polymorphisms of DNA repair genes play a potential role in the development, progression, and survival of Korean HCC patients with chronic HBV infection.
Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
Seok Won
SW
Jung
Neung Hwa
NH
Park
Jung Woo
JW
Shin
Bo Ryung
BR
Park
Chang Jae
CJ
Kim
Jong-Eun
JE
Lee
Eun-Soon
ES
Shin
Jeong A
JA
Kim
Young-Hwa
YH
Chung
D044466:Asian People / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D045647:DNA Glycosylases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D056910:Republic of Korea; D014157:Transcription Factors / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1; D000099250:DNA Excision Repair Protein ERCC-5
D045647:DNA Glycosylases; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D000076105:X-ray Repair Cross Complementing Protein 1; D000099250:DNA Excision Repair Protein ERCC-5; C000619371:XRCC1 protein, human; C101467:XRCC4 protein, human; C479058:oxoguanine glycosylase 1, human