中国广西人群中XRCC3密码子241多态性与黄曲霉毒素B1相关性肝细胞癌

The polymorphism of XRCC3 codon 241 and AFB1-related hepatocellular carcinoma in Guangxi population, China.

作者信息

Long Xi Dai, Ma Yun, Qu De Ying, Liu Yun Guang, Huang Zhao Quan, Huang Yong Zhi, Lin Zhong Hui, Wei Ni Bo, Zhou Shu Chun

机构信息

Department of Pathology, Youjiang Medical College for Nationalities, Baise, Guangxi Zhuang Autonomous Region, China.

出版信息

Ann Epidemiol. 2008 Jul;18(7):572-8. doi: 10.1016/j.annepidem.2008.03.003. Epub 2008 May 27.

DOI:10.1016/j.annepidem.2008.03.003

PMID:18504145

Abstract

PURPOSE

The relationship between aflatoxin B1 (AFB1) exposure and hepatocellular carcinoma (HCC) has been previously demonstrated and supported with strong epidemiological evidence. However, the role of genetic polymorphism of X-ray cross-complementing group 3 (XRCC3) codon 241 (namely: Thr241Met), which may be involved in the repair of DNA double-strand breaks caused by carcinogens such as AFB1, been less well elaborated.

METHODS

We conducted a case-control study including 491 cases and 862 controls to evaluate the associations between this polymorphism and HCC risk for Guangxi population by means of polymerase chain reaction-restriction fragment length polymorphism analysis.

RESULTS

We found that individuals with the XRCC3 genotypes with codon 241 Met (namely XRCC3-TM or XRCC3-MM) had an increased risk of HCC than those with the homozygote of XRCC3 codon 241 Thr alleles (namely XRCC3-TT, adjusted odds ratios 2.22 and 7.19; 95% confidence intervals 1.72-2.88 and 4.52-11.42, respectively). The risk of HCC, moreover, did appear to differ more significantly among individuals featuring high-level AFB1-DNA adducts, whose adjusted odds ratios (95% confidence intervals) were 11.59 (5.73-23.47) and 37.54 (16.32-86.32), respectively.

CONCLUSIONS

These findings support the hypothesis that the XRCC3 Thr241Met polymorphism may be associated with the risk of AFB1-related HCC among the Guangxi population.

摘要

目的

黄曲霉毒素B1（AFB1）暴露与肝细胞癌（HCC）之间的关系先前已得到证实，并得到了有力的流行病学证据支持。然而，X射线交叉互补修复基因3（XRCC3）密码子241（即：Thr241Met）的基因多态性作用，可能参与由AFB1等致癌物引起的DNA双链断裂修复，尚未得到充分阐述。

方法

我们进行了一项病例对照研究，包括491例病例和862例对照，通过聚合酶链反应-限制性片段长度多态性分析，评估广西人群中这种多态性与HCC风险之间的关联。

结果

我们发现，密码子241为Met的XRCC3基因型个体（即XRCC3-TM或XRCC3-MM）患HCC的风险高于密码子241为Thr等位基因纯合子的个体（即XRCC3-TT，调整后的比值比分别为2.22和7.19；95%置信区间分别为1.72-2.88和4.52-11.42）。此外，在具有高水平AFB1-DNA加合物的个体中，HCC风险差异似乎更为显著，其调整后的比值比（95%置信区间）分别为11.59（5.73-23.47）和37.54（16.32-86.32）。