Dataset Information

Nucleotide excision repair pathway gene polymorphisms are associated with risk and prognosis of colorectal cancer.

ABSTRACT:

Background

Single nucleotide polymorphisms (SNPs) are universally present in nucleotide excision repair (NER) pathway genes, which could make impacts on colorectal carcinogenesis and prognosis.

Aim

To explore the association of all tagSNPs in NER pathway genes with colorectal cancer (CRC) risk and prognosis in a northern Chinese population by a two-stage case-control design composed of a discovery and validation stage.

Methods

Genotyping for NER SNPs was performed using kompetitive allele specific PCR. In the discovery stage, 39 tagSNPs in eight genes were genotyped in 368 subjects, including 184 CRC cases and 184 individual-matched controls. In the validation stage, 13 SNPs in six genes were analyzed in a total of 1712 subjects, including 854 CRC cases and 858 CRC-free controls.

Results

Two SNPs (XPA rs10817938 and XPC rs2607775) were associated with an increased CRC risk in overall and stratification analyses. Significant cumulative and interaction effects were also demonstrated in the studied SNPs on CRC risk. Another two SNPs (ERCC2 rs1052555 and ERCC5 rs2228959) were newly found to be associated with a poor overall survival of CRC patients.

Conclusion

Our findings suggest novel SNPs in NER pathway genes that can be predictive for CRC risk and prognosis in a large-scale Chinese population. The present study has referential values for the identification of all-round NER-based genetic biomarkers in predicting the susceptibility and clinical outcome of CRC.

SUBMITTER: Li YK

PROVIDER: S-EPMC6969885 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Nucleotide excision repair pathway gene polymorphisms are associated with risk and prognosis of colorectal cancer.

Li Yan-Ke YK Xu Qian Q Sun Li-Ping LP Gong Yue-Hua YH Jing Jing-Jing JJ Xing Cheng-Zhong CZ Yuan Yuan Y

World journal of gastroenterology 20200101 3

<h4>Background</h4>Single nucleotide polymorphisms (SNPs) are universally present in nucleotide excision repair (NER) pathway genes, which could make impacts on colorectal carcinogenesis and prognosis.<h4>Aim</h4>To explore the association of all tagSNPs in NER pathway genes with colorectal cancer (CRC) risk and prognosis in a northern Chinese population by a two-stage case-control design composed of a discovery and validation stage.<h4>Methods</h4>Genotyping for NER SNPs was performed using kom ...[more]

PMID: 31988591

Similar Datasets

Project description:Background: Reduced DNA repair capacity in nucleotide excision repair (NER) pathways owing to genetic variant may influence cancer susceptibility. According to published studies, variants of NER genes associations with colorectal cancer (CRC) risk were inconclusive. Thus, this meta-analysis aimed to explore the possible association. A trial sequence analysis (TSA) analysis was performed to control the risk of false positive or false negative. Methods: PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Network (CNKI), Wanfang Database and Scientific and Technical Journal Database (VIP) were searched to identify relative studies until April 2022. The association was assessed by odds ratio (OR) in Allele, homozygous, heterozygous, dominant, recessive, and over-dominant models. In addition, Begg's and Egger's tests, sensitivity analysis, subgroup analysis and TSA analysis were performed. Results: A total of 29 studies were eventually included in the meta-analysis, including 12,153 CRC patients and 14,168 controls. It showed that excision and repair cross complementary group 1 (ERCC1) rs11615 CC genotype decreased the risk of CRC, compared with TT genotype (CC vs. TT: OR = 0.816, 95% CI = 0.673-0.990, p = 0.039). For ERCC1 rs3212986, the significant impact was detected on increased the risk of CRC in the allele (OR = 1.267, 95% CI = 1.027-1.562, p = 0.027), homozygous (OR = 1.805, 95% CI = 1.276-2.553, p = 0.001), dominant (OR = 1.214, 95% CI = 1.012-1.455, p = 0.037) and recessive (OR = 1.714, 95% CI = 1.225-2.399, p = 0.002) models, especially in the Asian population. The results revealed the association of ERCC2 rs1799793 A allele with a higher risk of CRC (A vs. G: OR = 1.163, 95% CI = 1.021-1.325, p = 0.023). It also showed that ERCC5 rs17655 increased CRC risk in the allele (OR = 1.104, 95% CI = 1.039-1.173, p = 0.001), homozygous (OR = 1.164, 95% CI = 1.018-1.329, p = 0.026), heterozygous (OR = 1.271, 95% CI = 1.018-1.329, p < 0.001), dominant (OR = 1.241, 95% CI = 1.135-1.358, p < 0.001) and over-dominant (OR = 0.828, 95% CI = 0.762-0.900, p < 0.001) models, especially among Asians. Conclusion: This meta-analysis based on current evidence suggests that the significant association was observed between ERCC1 rs11615, ERCC1 rs3212986, ERCC2 rs1799793, and ERCC5 rs17655 and CRC susceptibility. However, given the limited sample size and the influence of genetic background, studies of a larger scale and well-designed are required to confirm the results.

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

Nucleotide excision repair pathway gene polymorphisms are associated with risk and prognosis of colorectal cancer.

Background

Aim

Methods

Results

Conclusion

Publications

Nucleotide excision repair pathway gene polymorphisms are associated with risk and prognosis of colorectal cancer.

Similar Datasets

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