Genetic variants in the nucleotide excision repair pathway genes and gastric cancer susceptibility in a southern Chinese population.
Genetic variants in the nucleotide excision repair pathway genes and gastric cancer susceptibility in a southern Chinese population.
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中国南方人群核苷酸切除修复途径基因的遗传变异与胃癌易感性。
DOI：
10.2147/cmar.s160080
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发表时间：
2018
影响因子：
3.3
通讯作者：
Jia WH
中科院分区：
文献类型：
--
作者：
He J;Zhuo ZJ;Zhang A;Zhu J;Hua RX;Xue WQ;Zhang SD;Zhang JB;Li XZ;Jia WH
潜在的功能多态性可以调节蛋白质活性和宿主的DNA修复能力，从而影响癌症易感性。核苷酸切除修复核心通路基因多态性与胃癌易感性的关系尚不清楚。在此，我们系统地分析了核苷酸切除修复途径中4个关键基因（XPA，ERCC 1，ERCC 2和ERCC 4）的9个多态性与中国人群（包括1142例患者和1173例对照）胃癌风险之间的关联。使用比值比（OR）和95%置信区间（CI）估计风险相关性。我们观察到ERCC 1 rs 2298881 CA变异基因型与胃癌风险增加相关（CA vs. CC：调整OR [AOR]=1.33，95%CI =1.09-1.62;显性模型：AOR=1.32，95%CI =1.10-1.60）。而ERCC 1 rs3212986 AA变异基因型是胃癌的保护性因素（AA vs. CC：AOR=0.73，95%CI =0.54-0.98;隐性模型：AOR=0.72，95%CI =0.54-0.96）。基于基因型的mRNA表达分析进一步表明rs 2298881 A等位基因与ERCC 1 mRNA表达降低相关。这些结果提示ERCC 1基因多态性可能影响中国汉族人群胃癌的发病风险。
Potentially functional polymorphisms can modulate protein activities and host’s DNA repair capacity, thereby influencing cancer susceptibility. The association of the polymorphisms in the nucleotide excision repair core pathway genes and gastric cancer susceptibility remains largely unknown. Here, we systematically analyzed the associations between nine polymorphisms in four key genes (XPA, ERCC1, ERCC2, and ERCC4) in the nucleotide excision repair pathway and gastric cancer risk in a Chinese population including 1142 patients and 1173 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the risk associations. We observed that ERCC1 rs2298881 CA variant genotype was associated with an increased gastric cancer risk (CA vs. CC: adjusted OR [AOR]=1.33, 95% CI=1.09–1.62; dominant model: AOR=1.32, 95% CI=1.10–1.60). However, ERCC1 rs3212986 AA variant genotype was identified as a protective factor for gastric cancer (AA vs. CC: AOR=0.73, 95% CI=0.54–0.98; recessive model: AOR=0.72, 95% CI=0.54–0.96). Genotype-based mRNA expression analysis further indicated that the rs2298881 A allele was associated with decreased ERCC1 mRNA expression. In all, these results indicated that the ERCC1 polymorphisms may affect the risk of gastric cancer in the Chinese Han population.