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中国南方人群核苷酸切除修复通路基因中的遗传变异与胃癌易感性

Genetic variants in the nucleotide excision repair pathway genes and gastric cancer susceptibility in a southern Chinese population.

作者信息

He Jing, Zhuo Zhen-Jian, Zhang Anqi, Zhu Jinhong, Hua Rui-Xi, Xue Wen-Qiong, Zhang Shao-Dan, Zhang Jiang-Bo, Li Xi-Zhao, Jia Wei-Hua

机构信息

State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.

Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.

出版信息

Cancer Manag Res. 2018 Apr 12;10:765-774. doi: 10.2147/CMAR.S160080. eCollection 2018.

Abstract

BACKGROUND

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.

METHODS

Here, we systematically analyzed the associations between nine polymorphisms in four key genes (, , , and ) 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.

RESULTS

We observed that 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, 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 mRNA expression.

CONCLUSION

In all, these results indicated that the polymorphisms may affect the risk of gastric cancer in the Chinese Han population.

摘要

背景

潜在的功能性多态性可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途径基因中的多态性与胃癌易感性之间的关联在很大程度上仍不清楚。

方法

在此,我们系统分析了核苷酸切除修复途径中四个关键基因( 、 、 和 )的九个多态性与中国人群胃癌风险之间的关联,该人群包括1142例患者和1173例对照。采用比值比(OR)和95%置信区间(CI)来估计风险关联。

结果

我们观察到rs2298881的CA变异基因型与胃癌风险增加相关(CA与CC相比:调整后的OR [AOR]=1.33,95% CI=1.09 - 1.62;显性模型:AOR=1.32,95% CI=1.10 - 1.60)。然而,rs3212986的AA变异基因型被确定为胃癌的保护因素(AA与CC相比: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,rs2298881的A等位基因与 mRNA表达降低相关。

结论

总之,这些结果表明 多态性可能影响中国汉族人群的胃癌风险。

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