上海交通大学学报(医学版)

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XRCC4与XPC编码区突变与肝细胞癌的关联性研究

黄小英1,王 超1,黄炳臣1,姚金光1,黄永秩1,曾丽霞2,马 韵3,夏 强4,龙喜带1,4   

  1. 1.右江民族医学院附属医院病理科, 百色 533000; 2. 广西医科大学附属肿瘤医院病理科, 南宁 530021; 3.广西医科大学附属医院病理科, 南宁 530021; 4.上海交通大学 医学院附属仁济医院肝脏外科, 上海 200127
  • 出版日期:2013-08-28 发布日期:2013-09-16
  • 通讯作者: 龙喜带, 电子信箱: sjtulongxd@263.net。
  • 作者简介:黄小英(1971—), 女, 壮族, 副教授, 学士; 电子信箱: gxhxy3770@aliyun.com。
  • 基金资助:

    国家自然科学基金(81160255);广西自然科学基金(2013GXNSFAA019251);上海市教委科研创新项目(13YZ035);广西教育厅科研创新项目(201204LX674)

Correlation of mutations at coding regions of XRCC4 and XPC with hepatocellular carcinoma

HUANG Xiao-ying1, WANG Chao1, HUANG Bing-chen1, YAO Jin-guang1, HUANG Yong-zhi1, ZENG Li-xia2, MA Yun3, XIA Qiang4, LONG Xi-dai1,4   

  1. 1.Department of Pathology, Youjiang Medical College for Nationalities, Baise 533000, China; 2.Department of Pathology, the Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China; 3.Department of Pathology, the Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; 4.Department of Liver Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
  • Online:2013-08-28 Published:2013-09-16
  • Supported by:

    National Natural Science Foundation of China, 81160255; Guangxi Natural Science Foundation, 2013GXNSFAA019251; Innovation Program of Shanghai Education Committee, 13YZ035; Innovation Program of Guangxi Education Department, 201204LX674

摘要:

目的 探讨DNA修复基因XRCC4和XPC编码区突变对黄曲霉毒素B1(AFB1)相关性肝细胞癌(HCC)发病与预后的影响。方法 通过以医院为基础的病例—对照研究方式,采用TaqMan-聚合酶链反应(TaqMan-PCR)技术分析1 499例HCC患者和2 045名对照者XRCC4第247密码子及XPC第939密码子的基因型,以二分类logistic回归和Cox比例风险模型分析XRCC4和XPC编码区突变与AFB1相关性HCC发病和预后的关系。结果 ①XRCC4和XPC编码区多态性增加HCC的发病风险(P<0.05),风险值分别为2.01和1.76;②XRCC4和XPC突变基因型与AFB1暴露在HCC发病中存在相乘交互作用;③XRCC4和XPC突变基因型调节HCC的预后。结论 XRCC4和XPC编码区突变增加AFB1相关性HCC的发病风险,并影响HCC的预后。

关键词: 肝细胞癌, 黄曲霉毒素B1, XRCC4, XPC, 突变

Abstract:

Objective To investigate the effects of mutations at coding regions of X-ray repair complementing group 4 (XRCC4) and xeroderma pigmentosum group C (XPC) on the development and prognosis of hepatocellular carcinoma (HCC) related to aflatoxin B1(AFB1) exposure. Methods This study, including 1 499 HCC cases of HCC and 2 049 controls, was a hospital-based case-control study. TaqMan-PCR technique was employed to test genotypes of XRCC4 codon 247 and XPC codon 939, whereas logistic regression model and Cox's regression model were used to analyse the correlation of XRCC4 and XPC mutations with development and prognosis of AFB1-related HCC. Results The mutations at coding regions of XRCC4 and XPC gene increased the risk of development of HCC, with relative odd ratios of 2.01 and 1.76 for XRCC4 and XPC respectively (P<0.05). The mutative genotypes of XRCC4 and XPC genes interacted with AFB1 exposure in development of HCC. Furthermore, the mutative genotypes of these two genes modified the prognosis of HCC. Conclusion The mutations at coding regions of XRCC4 and XPC may increase the risk of development of AFB1-related HCC and modulate the prognosis of HCC.

Key words: hepatocellular carcinoma, aflatoxin B1, XRCC4, XPC, mutation