hEXO1基因单核苷酸多态性与肝细胞癌的相关性研究

覃若云; 谭盛葵; 仇小强; 谭超; 刘柳; 黄雄; 李岸花; 龙静铧; 廖倩; 杨筱筠

doi:10.16462/j.cnki.zhjbkz.2016.02.003

hEXO1基因单核苷酸多态性与肝细胞癌的相关性研究

doi: 10.16462/j.cnki.zhjbkz.2016.02.003

1. 广西医科大学公共卫生学院流行病学教研室, 广西南宁 530021;
2. 桂林医学院公共卫生学院流行病学教研室, 广西桂林 541004

基金项目:

国家自然科学基金（81160359）；广西自然科学基金（2012GXNSFAA053149）

详细信息

作者简介:
覃若云(1989－),女,广西贵港人,在读硕士研究生。主要研究方向:慢性病流行病学。

中图分类号: R730.267;R363.25
计量
- 文章访问数: 328
- HTML全文浏览量: 63
- PDF下载量: 355
- 被引次数: 0
出版历程
- 收稿日期: 2015-11-03
- 修回日期: 2016-01-02

Association of hEXO1 gene polymorphism with hepatocellular carcinoma

1. Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, China;
2. Department of Epidemiology, School of Public Health, Guilin Medical University, Guilin 541004, China

摘要

摘要: 目的探讨肝细胞癌（hepatocellular carcinoma，HCC）遗传易感性与人类核酸外切酶1（human exonuclease 1，hEXO1）基因多态性的相关性。方法应用病例对照方法，分别选取1 199例无HCC患者作为对照组，1 196例HCC患者作为病例组。选取hEXO1 基因的rs1047840、rs1776148位点进行基因分型，采取高通量 TaqMan MGB 实时荧光定量聚合酶链式反应（real-time fluorescent quantitative polymerase chain reaction，RT-PCR）进行基因分型。HCC 发病风险与位点rs1047840、rs1776148单核苷酸多态性（single nucleotide polymorphism，SNP）的相关性应用二分类Logistic 回归模型进行分析，同时研究吸烟、饮酒、乙型肝炎病毒（hepatitis B virus，HBV）感染等环境因素与位点rs1047840、rs1776148多态性的交互作用。结果位点rs1047840、rs1776148基因型在对照组、病例组的分布差异均无统计学意义（均有P>0.05）。经分层分析，rs1047840、rs1776148与 HCC 发病风险均无统计学关联（均有P>0.05）。交互作用分析结果显示，位点rs1047840、rs1776148基因多态性与吸烟、饮酒、HBV 感染均存在交互作用。结论饮酒、吸烟、HBV 感染等环境危险因素与rs1047840、rs1776148的交互作用可能与 HCC 发生有关。
- 癌,肝细胞 /
- 疾病遗传易感性 /
- 多态性,单核苷酸
Abstract: Objective To investigate the association between the human outer endonuclease 1 (human exonuclease 1, hEXO1) gene polymorphism and its susceptibility to hepatocellular carcinoma(HCC). Methods A case-control study was conducted in 1 199 non-tumors cases as controls, 1 196 cases with HCC patients as cases. The cases and controls were frequency matched in genders,age and nations.High flux TaqMan MGB real-time quantitative polymerase chain reaction (RT-PCR) technique was applied to genotyping for rs1047840, rs1776148 of hEXO1 gene. The binary unconditioned Logistic regression model was adopted to analyze the association between the rs1047840, rs1776148 single nucleotide polymorphisms (SNP) and the risk of HCC,as well as to evaluate the interaction between the SNPs and the environmental factors.Results Distributions of genetypes for rs1047840, rs1776148 in the cases and the controls had no statistically significant differences (all P>0.05). The results of stratification analyses indicated that rs1047840, rs1776148 in the cases and the controls had no statistically significant differences (all P>0.05). Interaction analyses indicated that rs1047840, rs1776148 was significantly associated with the risk of HCC.Conclusions Interactions among polymorphisms of rs1047840, rs1776148 and drinking, smoking, HBV infection is associated with the occurrence of HCC.
- Carcinoma, hepatocellular /
- Genetic predisposition to disease /
- Polymorphism, single nucleotide

HTML全文

参考文献(16)

Bosetti C, Turati F, La Vecchia C, et al. Hepatocellular carcinoma epidemiology [J]. Best Pract Res Clin Gastroenterol, 2014,28(5):753-770.

Muro Y, Sugiura K, Mimor T, et al. DNA mismatch repair enzymes: genetic defects and autoimmunity [J]. Clin Chim Acta, 2015,442:102-109.

Orans J, Mcsweeney EA, Iyer RR, et al. Structures of human exonuclease 1 DNA complexes suggest a unified mechanism for nuclease family [J]. Cell, 2011,145(2):212-223.

Nielsen FC, Jäger AC, Lützen A, et al. Characterization of human exonuclease 1 in complex with mismatch repair proteins, subcellular localization and association with PCNA [J]. Oncogene, 2004,23(7):1457-1468.

Tishkoff DX, Amin NS, Viars CS, et al. Identification of a human gene encoding a homologue of Saccharomyces cerevisiae EXO1, an exonuclease implicated in mismatch repair and recombination [J]. Cancer Res, 1998,58(22):5027-5031.

Sun X, Zheng L, Shen B. Functional alterations of human exonuclease 1 mutants identified in atypical hereditary nonpolyposis colorectal cancer syndrome [J]. Cancer Res, 2002,62(21):6026-6030.

Hansen LT, Thykjaer T, Ørntoft TF, et al. The role of mismatch repair in small-cell lung cancer cells [J]. Eur J Cancer, 2003,39(10):1456-1467.

Thompson E, Meldrum CJ, Crooks R. Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations [J]. Clin Genet, 2003,65(3):215-225.

Bak ST, Sakellariou D, Pena-Diaz J. The dual nature of mismatch repair as antimutator and mutator: for better or for worse [J]. Front Genet, 2014,5:287.

Ladd PD, Wilson DM, Kelley MR. Identification of the human HEX1/hExo1 gene promoter and characterization of elements responsible for promoter activity [J]. DNA Repair (Amst), 2003,2(2):187-198

Jäger AC, Rasmussen M, Bisgaard HC, et al. HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence assembly of hMutLalpha and hMLH1-hEXO1 complexes [J]. Oncogene, 2001,20(27):3590-3595.

Thompson E, Meldrum CJ, Crooks R, et al. Hereditary nonpolyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations[J]. Clin Genet, 2004,65(3): 215-225.

Wu Y, Berends MJ, Post JG, et al. Germline mutations of Exo1 gene in patients with hereditary nonpolyposis colorectal cancer (HNPCC) and atypical HNPCC forms [J]. Gastroenterology, 2001,120(7):1580-1587.

Jin G, Wang H, Hu Z.Potentially functional polymorphisms of EXO1 and risk of lung cancer in a Chinese population: a case－control analysis [J]. Lung Cancer, 2008, 60(3): 340-346.

谭盛葵,仇小强,余红平,等. 广西肝癌高发区原发性肝癌危险因素 Logistic 回归分析 [J]. 华夏医学, 2008,21(1):29-31.

Miyata M, Morishita A, Sakamoto T, et al.MicroRNA profiles in cisplatin-induced apoptosis of hepatocellular carcinoma cells [J]. Int J Oncol, 2015,47(2):535-542.

施引文献

资源附件(0)

访问统计