意大利人群中XRCC1基因Arg399Gln多态性与肝细胞癌风险

XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma risk in the Italian population.

作者信息

Santonocito Concetta, Scapaticci Margherita, Nedovic Bojan, Annicchiarico Eleonora B, Guarino Donatella, Leoncini Emanuele, Boccia Stefania, Gasbarrini Antonio, Capoluongo Ettore

机构信息

Laboratory of Clinical Molecular Biology, Department of Biochemistry & Clinical Biochemistry, Catholic University of the Sacred Heart, Rome - Italy.

Department of Internal Medicine, A. Gemelli Teaching Hospital, Catholic University of the Sacred Heart, Rome - Italy.

出版信息

Int J Biol Markers. 2017 May 4;32(2):e190-e194. doi: 10.5301/jbm.5000241.

DOI:10.5301/jbm.5000241

PMID:28058700

Abstract

BACKGROUND

The human X-ray repair cross-complementing protein 1 (XRCC1) gene encodes for one of the major repair factors involved in base excision repair (BER), which is reported to be associated with the risk of several cancers. A few studies have explored the association between risk of hepatocellular carcinoma (HCC) and single-nucleotide polymorphisms (SNPs) in different DNA repair genes, with contradictory results. The purpose of this study was to evaluate the association between XRCC1 Arg399Gln polymorphism and susceptibility to HCC.

METHODS

A total of 89 HCC patients and 99 randomly selected healthy controls were enrolled. Genotyping of XRCC1 rs25487 was performed by high-resolution melting analysis and Sanger sequencing.

RESULTS

On univariate analysis, a statistically significant association was found between risk of HCC and XRCC1 399Arg/Gln genotype (odd ratio [OR] = 1.88; 95% CI, 1.04-3.43), which was confirmed after adjusting by sex (OR = 1.94; 95% CI, 1.04-3.63). Although not significant, Kaplan-Meier analysis showed a decreased median survival in Arg/Gln genotype carriers in comparison with Arg/Arg carriers.

CONCLUSIONS

To our knowledge, this is the first study reporting an association between BER SNP and HCC risk in a population of central-southern Italy.

摘要

背景

人类X射线修复交叉互补蛋白1（XRCC1）基因编码参与碱基切除修复（BER）的主要修复因子之一，据报道该因子与多种癌症的风险相关。一些研究探讨了不同DNA修复基因中的单核苷酸多态性（SNP）与肝细胞癌（HCC）风险之间的关联，但结果相互矛盾。本研究的目的是评估XRCC1 Arg399Gln多态性与HCC易感性之间的关联。

方法

共纳入89例HCC患者和99例随机选择的健康对照。通过高分辨率熔解分析和桑格测序对XRCC1 rs25487进行基因分型。

结果

单因素分析发现，HCC风险与XRCC1 399Arg/Gln基因型之间存在统计学显著关联（比值比[OR]=1.88；95%置信区间，1.04-3.43），经性别调整后得到证实（OR=1.94；95%置信区间，1.04-3.63）。虽然不显著，但Kaplan-Meier分析显示，与Arg/Arg携带者相比，Arg/Gln基因型携带者的中位生存期缩短。