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COX-2 gene rs689466 polymorphism is associated with increased risk of colorectal cancer among Caucasians: a meta-analysis.

ABSTRACT: BACKGROUND:Several studies have reported the Cyclooxygenase 2 (COX-2) rs689466 polymorphism as a susceptibility locus of colorectal cancer (CRC), but their findings are inconsistent. Thus, this meta-analysis was performed to more accurately identify the effects of this polymorphism on CRC risk. METHODS:Potential case-control studies on EMBASE, Google Scholar, Web of Science, Cochrane Library, and PubMed were searched. The strength of association was quantified by pooled odds ratio and 95% confidence interval. Totally 16 articles involving 8998 cases and 11,917 controls were included. RESULTS:None of the five tested genetic models revealed an association between rs689466 polymorphism and CRC risk. Stratified analysis by ethnicity uncovered a positive association between this polymorphism and higher CRC risk in Caucasians, but not in Asians. In addition, we found that high expression of COX-2 was associated with better overall survival for all CRC patients. CONCLUSION:To sum up, the COX-2 rs689466 polymorphism may be related with susceptibility to CRC in Caucasians. This finding should be verified by larger-size studies with different ethnic groups.

SUBMITTER: Zhang YC

PROVIDER: S-EPMC7391579 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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COX-2 gene rs689466 polymorphism is associated with increased risk of colorectal cancer among Caucasians: a meta-analysis.

Zhang Yong-Chen YC Zhao Hui H Chen Chen C Ali Mohammad Amzad MA

World journal of surgical oncology 20200730 1

<h4>Background</h4>Several studies have reported the Cyclooxygenase 2 (COX-2) rs689466 polymorphism as a susceptibility locus of colorectal cancer (CRC), but their findings are inconsistent. Thus, this meta-analysis was performed to more accurately identify the effects of this polymorphism on CRC risk.<h4>Methods</h4>Potential case-control studies on EMBASE, Google Scholar, Web of Science, Cochrane Library, and PubMed were searched. The strength of association was quantified by pooled odds ratio ...[more]

PMID: 32731879

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Project description:We investigated single nucleotide polymorphism (SNP) of the betaglycan gene (TGFBR3) encoding the TGFβ co-receptor in endometrial cancer (EC) and its association with betaglycan expression. The study group included 153 women diagnosed with EC and 248 cancer-free controls. SNP genotyping and gene expression were analyzed using TaqMan probes. Three out of the eight SNPs tested, i.e., rs12566180 (CT; OR = 2.22; 95% CI = 1.15-4.30; p = 0.0177), rs6680463 (GC; OR = 2.34; 95% CI = 1.20-4.53; p = 0.0120) and rs2296621 (TT; OR = 6.40; 95% CI = 1.18-34.84; p = 0.0317) were found to be significantly associated with increased risk of EC (adjusted to age, body mass index, menarche and parity). Among the analyzed SNPs, only rs2296621 demonstrated the impact on the increased cancer aggressiveness evaluated by the WHO grading system (G3 vs. G1/2, GT-OR = 4.04; 95% CI = 1.56-10.51; p = 0.0026; T-OR = 2.38; 95% CI = 1.16-4.85; p = 0.0151). Linkage disequilibrium (LD) analysis revealed high LD (r2 ≥ 0.8) in two haploblocks, constructed by rs2770186/rs12141128 and rs12566180/rs6680463, respectively. In the case of C/C haplotype (OR = 4.82; 95% CI = 1.54-15.07; p = 0.0116-Bonferroni corrected) and T/G haplotype (OR = 3.25; 95% CI = 1.29-8.15; p = 0.0328-Bonferroni corrected) in haploblock rs12566180/rs6680463, significantly higher frequency was observed in patients with EC as compared to the control group. The genotype-phenotype studies showed that SNPs of the TGFBR3 gene associated with an increased risk of EC, i.e., rs12566180 and rs2296621 may affect betaglycan expression at the transcriptomic level (rs12566180-CC vs. TT, p < 0.01; rs2296621-GG vs. TT, p < 0.001, GT vs. TT, p < 0.05). Functional consequences of evaluated TGFBR3 gene SNPs were supported by RegulomeDB search. In conclusion, polymorphism of the TGFBR3 gene may be associated with an increased EC occurrence, as well as may be the molecular mechanism responsible for observed betaglycan down-regulation in EC patients.

Dataset Information

COX-2 gene rs689466 polymorphism is associated with increased risk of colorectal cancer among Caucasians: a meta-analysis.

Publications

COX-2 gene rs689466 polymorphism is associated with increased risk of colorectal cancer among Caucasians: a meta-analysis.

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