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

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 (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. Results: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. Conclusion:In all, these results indicated that the ERCC1 polymorphisms may affect the risk of gastric cancer in the Chinese Han population.

SUBMITTER: He J

PROVIDER: S-EPMC5903836 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

He Jing J Zhuo Zhen-Jian ZJ Zhang Anqi A Zhu Jinhong J Hua Rui-Xi RX Xue Wen-Qiong WQ Zhang Shao-Dan SD Zhang Jiang-Bo JB Li Xi-Zhao XZ Jia Wei-Hua WH

Cancer management and research 20180412

<h4>Background</h4>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.<h4>Methods</h4>Here, we systematically analyzed the associations between nine polymorphisms in four key genes (<i>XPA</i>, <i>ERCC1</i>, <i>ERCC2</i>, and <i>ERCC4</i>) in the nucleotide e ...[more]

PMID: 29695933

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Project description:Polymorphisms of NER genes could change NER ability, thereby altering individual susceptibility to GC. We systematically analyzed 39 SNPs of 8 key genes of NER pathway in 2686 subjects including 898 gastric cancer (GC), 851 atrophic gastritis (AG) and 937 controls (CON) in northern Chinese. SNP genotyping were performed using Sequenom MassARRAY platform. The results demonstrated that DDB2 rs830083 GG genotype was significantly associated with increased GC risk compared with wild-type CC (OR=2.32, P= 6.62 × 10-9); XPC rs2607775 CG genotype conferred a 1.73 increased odds of GC risk than non-cancer subjects compared with wild-type CC (OR=1.73, P= 3.04 × 10-4). The combined detection of these two polymorphisms demonstrated even higher GC risk (OR=3.05). Haplotype analysis suggested that DDB2 rs2029298-rs326222-rs3781619-rs830083 GTAG haplotype was significantly associated with disease risk in each step of CON→AG→GC development (AG vs. CON: OR=2.88, P= 7.51 × 10-7; GC vs. AG: OR=2.90, P=5.68 × 10-15; GC vs. CON: OR=8.42, P=2.22 × 10-15); DDB2 GTAC haplotype was associated with reduced risk of GC compared with CON (OR=0.63, P= 8.31 × 10-12). XPC rs1870134-rs2228000-rs2228001-rs2470352-rs2607775 GCAAG haplotype conferred increased risk of GC compared with AG (OR=1.88, P= 6.98 × 10-4). XPA rs2808668 and drinking, DDB2 rs326222, rs3781619, rs830083 and smoking demonstrated significant interactions in AG; XPC rs2607775 had significant interaction with smoking in GC. In conclusion, NER pathway polymorphisms especially in "damage incision" step were significantly associated with GC risk and had interactions with environment factors. The detection of NER pathway polymorphisms such as DDB2 and XPC might be applied in the prediction of GC risk and personalized prevention in the future. NER pathway polymorphisms especially in "damage incision" step were significantly associated with GC risk and had interactions with environment factors, which might be applied in the prediction of GC risk and personalized prevention in the future.

Dataset Information

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

Publications

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

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