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The association of polymorphisms in nucleotide excision repair genes with ovarian cancer susceptibility.

ABSTRACT: Nucleotide excision repair (NER), the core mechanism of DNA repair pathway, was commonly used to maintain genomic stability and prevent tumorigenesis. Previous investigations have demonstrated that single nucleotide polymorphisms (SNPs) of NER pathway genes were associated with various types of cancer. However, there was no research elucidating the genetic association of entire NER pathway with ovarian cancer susceptibility. Therefore, we conducted genotyping for 17 SNPs of six NER core genes (XPA, XPC, XPG, ERCC1, ERCC2, and ERCC4) in 89 ovarian cancer cases and 356 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of association. The result showed that both ERCC1 rs11615 and XPC rs2228000 were significantly associated with reduced risk of ovarian cancer under dominant genetic model (adjusted OR = 0.35, 95% CI = 0.20-0.61, P=0.0002 and adjusted OR = 0.49, 95% CI = 0.30-0.81, P=0.005 respectively). In addition, XPC rs2228001 and ERCC2 rs238406 had statistically significant association with the increased risk of ovarian cancer under dominant genetic model (adjusted OR = 1.72, 95% CI = 1.02-2.92, P=0.043 and adjusted OR = 2.07, 95% CI = 1.07-4.01, P=0.032 respectively). ERCC1 rs3212986 were related with the increased risk of ovarian cancer under recessive model (adjusted OR = 2.40, 95% CI = 1.30-4.44, P=0.005). In conclusion, our results indicated that ERCC1, XPC and ERCC2 might influence ovarian cancer susceptibility. Further research with large sample size is warranted to validate the reliability and accuracy of our results.

SUBMITTER: Zhao Z

PROVIDER: S-EPMC6013708 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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The association of polymorphisms in nucleotide excision repair genes with ovarian cancer susceptibility.

Zhao Zhiguang Z Zhang Anqi A Zhao Yuan Y Xiang Junmiao J Yu Danyang D Liang Zongwen Z Xu Chaoyi C Zhang Qiong Q Li Jianmin J Duan Ping P

Bioscience reports 20180621 3

Nucleotide excision repair (NER), the core mechanism of DNA repair pathway, was commonly used to maintain genomic stability and prevent tumorigenesis. Previous investigations have demonstrated that single nucleotide polymorphisms (SNPs) of NER pathway genes were associated with various types of cancer. However, there was no research elucidating the genetic association of entire NER pathway with ovarian cancer susceptibility. Therefore, we conducted genotyping for 17 SNPs of six NER core genes (< ...[more]

PMID: 29669843

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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

The association of polymorphisms in nucleotide excision repair genes with ovarian cancer susceptibility.

Publications

The association of polymorphisms in nucleotide excision repair genes with ovarian cancer susceptibility.

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