Research ArticlePolymorphisms of DNA repair genes in Korean hepatocellular carcinoma patients with chronic hepatitis B: Possible implications on survival
Introduction
Chronic hepatitis B virus (HBV) infection is one of the established etiologic agents of hepatocelluar carcinoma (HCC) worldwide, which contributes to the development of the majority of HCC cases in Korea [1], [2]. However, only a small proportion of chronic HBV carriers develop HCC in their lifetime, suggesting that other risk factors may contribute to the inter-individual variation in susceptibility to hepatocarcinogenesis [3]. In addition, various genetic factors appear to influence the outcome of HBV infections [4], [5], [6]. Based on the current knowledge of cancer molecular pathogenesis, polymorphic variations such as single nucleotide polymorphism (SNP) within several gene classes are considered to be important for tumor development.
It is suggested that the majority of HCC cases result from DNA damage caused by hepatitis viruses; this is the major underlying factor that predisposes to the development of HCC [7]. Damage resulting from endogenous or exogenous exposure may be repaired by enzymes encoded by one or more DNA repair pathways. In humans, more than 70 genes are involved in the five main DNA repair pathways: base excision repair (BER), nucleotide excision repair (NER), mismatch repair, homologous recombination repair, and non-homologous end joining (NHEJ). Defective DNA repair can lead to the accumulation of mutations and microsatellite instability in the genome, increasing the chance of malignant transformation [8]. Genetic variation may alter the function of DNA repair proteins, influencing the risk of development and clinical outcomes of HCC.
Although many studies have been published on the associations between SNPs of DNA repair genes and the risk of various cancers [9], few studies have reported on the associations between SNPs of DNA repair genes and HCC. In this study, we investigated the association between selective SNPs of DNA repair genes and the risk of HCC development and its clinical outcomes.
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Study population
Patients with HCC were recruited consecutively from two hospitals (Asan Medical Center and Ulsan University Hospital) in Korea from 1999 to 2010. A total of 708 Korean patients who were hepatitis B virus surface antigen (HBsAg) carriers with HCC were included. The diagnosis of HCC was made by liver biopsy or the combination of increased alpha-fetoprotein (AFP of ⩾200 ng/ml) and the typical vascular pattern on angiography or dynamic imaging [10]. The control group consisted of 388 inactive HBsAg
Characteristics of the study population
The age and gender distributions of the studied population were similar between HCC cases and controls. The mean age at enrollment was 53.3 for the cases and 52.6 years for the control group. The male/female ratio was also similar between HCC patients and controls (582:126 vs. 322:66, p = 0.803). The patient characteristics and clinicopathologic features of the tumor are summarized in Table 2. Of the 708 patients, 314 had their primary tumor surgically resected; the remaining 394 patients
Discussion
In this study, we evaluated the effect of 14 SNPs of eight DNA repair genes on the development, tumor progression, and overall survival of patients with HBV-associated HCC. To the best of our knowledge, this is the first study to describe the association between SNPs of DNA repair genes and clinical outcomes of HCC. We demonstrated that the XRCC4 rs1805377 variant genotype was significantly associated with the development of HCC. Moreover, the SNP of XRCC4 rs1805377, both alone and in
Financial support
This study was supported by Priority Research Center Program through National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology 2009-0094053.
Conflict of interest
The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
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Genetic polymorphisms in DNA repair genes and hepatocellular carcinoma risk
2021, DNA RepairCitation Excerpt :Additionally, haplotype analysis of XRCC5 showed that, AA in block 1 (composed of rs828704 and rs16855458) and CGGTT in block 2 (composed of rs668844, rs207916, rs3770502, rs9288516 and rs1051677) were associated with decreased risk of HCC compared with the most common haplotypes [151]. For XRCC5 rs3835 polymorphism, Jung and colleagues investigated its association with the risk of HCC in Korean population but demonstrated no significant association [40]. Furthermore, no significant relation between XRCC5 rs80309960 polymorphism and risk of HCC induced by AFB1 exposure was found by Long et al. in Chinese population [145].
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