Associations between three XRCC1 polymorphisms and hepatocellular carcinoma risk: A meta-analysis of case-control studies.

Yao Xiong,Lianying Ge,Shan Pan,Jiaxiang Ye,Qian Zhang,Qingyi Wei

doi:10.1371/journal.pone.0206853

Abstract

Conflicting results have been obtained regarding the association between X-ray repair cross complementation group 1 (XRCC1) and susceptibility to hepatocellular carcinoma (HCC). In this study, associations between HCC and three polymorphisms (Arg194Trp, Arg280His, and Arg399Gln) were evaluated using a meta-analysis approach. PubMed, Web of Science, Cochrane Library, the Chinese National Knowledge Infrastructure, and the Wanfang standard database were systematically searched to identify all relevant case-control studies published through March 2018. A total of 32 case-control studies, including 13 that evaluated Arg194Trp, 14 that evaluated Arg280His, and 26 that evaluated Arg399Gln, were analyzed. In the entire study population, XRCC1 Arg399Gln was significantly associated not only with overall risk of HCC (homozygous model, OR = 1.61, 95% CI: 1.40–1.85, P < 0.05; recessive model, OR = 1.40, 95% CI: 1.23–1.59, P < 0.05) but also with the risk of HCC in Chinese patients (homozygous model, OR = 1.78, 95% CI: 1.53–2.08, P < 0.05; recessive model, OR = 1.47, 95% CI: 1.27–1.70, P < 0.05). Limiting the analysis to studies demonstrating Hardy–Weinberg equilibrium (HWE), the results were consistent and robust. Similarly, a significant association between XRCC1 Arg399Gln and HCC risk was found in healthy controls in the general population but not in hospital controls. Trial sequential analysis (TSA), false-positive report probabilities (FPRP), and combined genotype analysis revealed that XRCC1 Arg399Gln is mainly associated with susceptibility to liver cancer. However, there was no association between Arg194Trp or Arg280His and the risk of HCC. These results, indicating that the Arg399Gln polymorphism of XRCC1 is associated with the risk of HCC in the Chinese population, provide a basis for the development of improved detection and treatment approaches.

Highlights

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that ranks second in cancer deaths in developing countries, sixth in cancer deaths in developed countries [1], and third in the incidence of malignant tumors in China [2]
A comprehensive search was performed against various databases, i.e., PubMed, Web of Science, Cochrane Library, the Chinese National Knowledge Infrastructure, and the Wanfang standard database, to identify case–control studies published through March 1, 2018 that examined the association between X-ray repair cross complementation group 1 (XRCC1) polymorphisms and hepatocellular carcinoma (HCC) risk
The XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphisms were evaluated by calculating ORs and 95% CIs under homozygous, heterozygous, dominant, and recessive models

Summary

Introduction

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that ranks second in cancer deaths in developing countries, sixth in cancer deaths in developed countries [1], and third in the incidence of malignant tumors in China [2]. The onset of HCC is occult, and early symptoms and signs are not easy to detect. Most patients are diagnosed with advancedstage disease; treatment is not effective. According to recent epidemiological data, the 5-year survival rate of patients with HCC is only 18% [1]. To improve the prevention and treatment of HCC, it is necessary to clarify its pathogenesis. The formation of HCC is a multistep process of multiple pathogenies. Not everyone exposed to these factors develops HCC. Increasing evidence suggests that HCC is triggered by external factors and by genetic factors

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Conclusion