XRCC1基因多态性与胰腺癌易感性的关联及基因内单核苷酸多态性相互作用

Association and Intragenic Single-Nucleotide Polymorphism Interactions of the XRCC1 Polymorphisms for Pancreatic Cancer Susceptibility.

作者信息

Hou Bao-Hua, Jian Zhi-Xiang, Cui Peng, Li Shao-Jie, Tian Rui-Qing, Ou Jin-Rui

机构信息

From the Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

出版信息

Pancreas. 2016 Apr;45(4):546-51. doi: 10.1097/MPA.0000000000000482.

DOI:10.1097/MPA.0000000000000482

PMID:26418909

Abstract

OBJECTIVES

X-ray repair cross-complementing group 1 (XRCC1) gene is an important candidate gene for influencing human cancer risks. This study examined the main and interactive effect of 9 single-nucleotide polymorphisms (SNPs) (Arg194Trp, Arg280His, Arg399Gln, c.1254C>T, c.1517G>C, c.1471G>A, C310T, 539del542, and T1915C) of XRCC1 in contribution to pancreatic cancer (PC).

METHODS

A total of 298 PC patients and 298 healthy controls were enrolled. Selected SNPs in XRCC1 were genotyped. The generalized multifactor dimensionality reduction method investigated gene-gene interactions.

RESULTS

Single-locus analyses showed that, in the codominant model, the GO genotype of 539del542 might have a higher risk for PC (odds ratio [OR], 1.47; 95% confidence interval [95% CI], 1.05-2.08). For T1915C polymorphism, the TC and CC genotypes both had a higher risk for PC (OR, 1.76; 95% CI, 1.25-2.48; OR, 1.83; 95% CI, 1.05-3.19, respectively); and a similar result was observed in the dominant model (OR, 1.77; 95% CI, 1.28-2.46). A tendency of association between Arg280His and PC was also detected in the dominant model (OR, 0.70; 95% CI, 0.48-1.00). Furthermore, the generalized multifactor dimensionality reduction method showed that the 4-locus model was significant, involving Arg280His, 539del542, T1915C, and c.1517G>C (P < 0.05).

CONCLUSIONS

Thus, XRCC1 polymorphisms may contribute to the risk of PC independently or in an interactive manner.

摘要

目的

X射线修复交叉互补基因1（XRCC1）是影响人类癌症风险的重要候选基因。本研究检测了XRCC1基因9个单核苷酸多态性（SNP）（Arg194Trp、Arg280His、Arg399Gln、c.1254C>T、c.1517G>C、c.1471G>A、C310T、539del542和T1915C）对胰腺癌（PC）的主要作用及交互作用。

方法

共纳入298例PC患者和298例健康对照。对XRCC1基因中选定的SNP进行基因分型。采用广义多因素降维法研究基因-基因相互作用。

结果

单基因座分析显示，在共显性模型中，539del542的GO基因型可能使PC发病风险更高（优势比[OR]，1.47；95%置信区间[95%CI]，1.05 - 2.08）。对于T1915C多态性，TC和CC基因型均使PC发病风险更高（OR分别为1.76；95%CI，1.25 - 2.48；OR，1.83；95%CI，1.05 - 3.19）；在显性模型中观察到类似结果（OR, 1.77；95%CI，1.28 - 2.46）。在显性模型中还检测到Arg280His与PC之间存在关联趋势（OR, 0.70；95%CI，0.48 - 壹.00）。此外，广义多因素降维法显示4个基因座的模型具有显著性，涉及Arg280His、539del542、T1915C和c.1517G>C（P < 0.05）。