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Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development
BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding mitotic kinases could influence development and progression of gastric cancer (GC). METHODS: Case-control study of nine SNPs in mitotic genes was conducted using qPCR. The study included 116 GC patients and 203 controls. In silico...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744709/ https://www.ncbi.nlm.nih.gov/pubmed/31521144 http://dx.doi.org/10.1186/s12885-019-6133-z |
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author | Mesic, Aner Rogar, Marija Hudler, Petra Bilalovic, Nurija Eminovic, Izet Komel, Radovan |
author_facet | Mesic, Aner Rogar, Marija Hudler, Petra Bilalovic, Nurija Eminovic, Izet Komel, Radovan |
author_sort | Mesic, Aner |
collection | PubMed |
description | BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding mitotic kinases could influence development and progression of gastric cancer (GC). METHODS: Case-control study of nine SNPs in mitotic genes was conducted using qPCR. The study included 116 GC patients and 203 controls. In silico analysis was performed to evaluate the effects of polymorphisms on transcription factors binding sites. RESULTS: The AURKA rs1047972 genotypes (CT vs. CC: OR, 1.96; 95% CI, 1.05–3.65; p = 0.033; CC + TT vs. CT: OR, 1.94; 95% CI, 1.04–3.60; p = 0.036) and rs911160 (CC vs. GG: OR, 5.56; 95% CI, 1.24–24.81; p = 0.025; GG + CG vs. CC: OR, 5.26; 95% CI, 1.19–23.22; p = 0.028), were associated with increased GC risk, whereas certain rs8173 genotypes (CG vs. CC: OR, 0.60; 95% CI, 0.36–0.99; p = 0.049; GG vs. CC: OR, 0.38; 95% CI, 0.18–0.79; p = 0.010; CC + CG vs. GG: OR, 0.49; 95% CI, 0.25–0.98; p = 0.043) were protective. Association with increased GC risk was demonstrated for AURKB rs2241909 (GG + AG vs. AA: OR, 1.61; 95% CI, 1.01–2.56; p = 0.041) and rs2289590 (AC vs. AA: OR, 2.41; 95% CI, 1.47–3.98; p = 0.001; CC vs. AA: OR, 6.77; 95% CI, 2.24–20.47; p = 0.001; AA+AC vs. CC: OR, 4.23; 95% CI, 1.44–12.40; p = 0.009). Furthermore, AURKC rs11084490 (GG + CG vs. CC: OR, 1.71; 95% CI, 1.04–2.81; p = 0.033) was associated with increased GC risk. A combined analysis of five SNPs, associated with an increased GC risk, detected polymorphism profiles where all the combinations contribute to the higher GC risk, with an OR increased 1.51-fold for the rs1047972(CT)/rs11084490(CG + GG) to 2.29-fold for the rs1047972(CT)/rs911160(CC) combinations. In silico analysis for rs911160 and rs2289590 demonstrated that different transcription factors preferentially bind to polymorphic sites, indicating that AURKA and AURKB could be regulated differently depending on the presence of particular allele. CONCLUSIONS: Our results revealed that AURKA (rs1047972 and rs911160), AURKB (rs2241909 and rs2289590) and AURKC (rs11084490) are associated with a higher risk of GC susceptibility. Our findings also showed that the combined effect of these SNPs may influence GC risk, thus indicating the significance of assessing multiple polymorphisms, jointly. The study was conducted on a less numerous but ethnically homogeneous Bosnian population, therefore further investigations in larger and multiethnic groups and the assessment of functional impact of the results are needed to strengthen the findings. |
format | Online Article Text |
id | pubmed-6744709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-67447092019-09-18 Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development Mesic, Aner Rogar, Marija Hudler, Petra Bilalovic, Nurija Eminovic, Izet Komel, Radovan BMC Cancer Research Article BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding mitotic kinases could influence development and progression of gastric cancer (GC). METHODS: Case-control study of nine SNPs in mitotic genes was conducted using qPCR. The study included 116 GC patients and 203 controls. In silico analysis was performed to evaluate the effects of polymorphisms on transcription factors binding sites. RESULTS: The AURKA rs1047972 genotypes (CT vs. CC: OR, 1.96; 95% CI, 1.05–3.65; p = 0.033; CC + TT vs. CT: OR, 1.94; 95% CI, 1.04–3.60; p = 0.036) and rs911160 (CC vs. GG: OR, 5.56; 95% CI, 1.24–24.81; p = 0.025; GG + CG vs. CC: OR, 5.26; 95% CI, 1.19–23.22; p = 0.028), were associated with increased GC risk, whereas certain rs8173 genotypes (CG vs. CC: OR, 0.60; 95% CI, 0.36–0.99; p = 0.049; GG vs. CC: OR, 0.38; 95% CI, 0.18–0.79; p = 0.010; CC + CG vs. GG: OR, 0.49; 95% CI, 0.25–0.98; p = 0.043) were protective. Association with increased GC risk was demonstrated for AURKB rs2241909 (GG + AG vs. AA: OR, 1.61; 95% CI, 1.01–2.56; p = 0.041) and rs2289590 (AC vs. AA: OR, 2.41; 95% CI, 1.47–3.98; p = 0.001; CC vs. AA: OR, 6.77; 95% CI, 2.24–20.47; p = 0.001; AA+AC vs. CC: OR, 4.23; 95% CI, 1.44–12.40; p = 0.009). Furthermore, AURKC rs11084490 (GG + CG vs. CC: OR, 1.71; 95% CI, 1.04–2.81; p = 0.033) was associated with increased GC risk. A combined analysis of five SNPs, associated with an increased GC risk, detected polymorphism profiles where all the combinations contribute to the higher GC risk, with an OR increased 1.51-fold for the rs1047972(CT)/rs11084490(CG + GG) to 2.29-fold for the rs1047972(CT)/rs911160(CC) combinations. In silico analysis for rs911160 and rs2289590 demonstrated that different transcription factors preferentially bind to polymorphic sites, indicating that AURKA and AURKB could be regulated differently depending on the presence of particular allele. CONCLUSIONS: Our results revealed that AURKA (rs1047972 and rs911160), AURKB (rs2241909 and rs2289590) and AURKC (rs11084490) are associated with a higher risk of GC susceptibility. Our findings also showed that the combined effect of these SNPs may influence GC risk, thus indicating the significance of assessing multiple polymorphisms, jointly. The study was conducted on a less numerous but ethnically homogeneous Bosnian population, therefore further investigations in larger and multiethnic groups and the assessment of functional impact of the results are needed to strengthen the findings. BioMed Central 2019-09-14 /pmc/articles/PMC6744709/ /pubmed/31521144 http://dx.doi.org/10.1186/s12885-019-6133-z Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Mesic, Aner Rogar, Marija Hudler, Petra Bilalovic, Nurija Eminovic, Izet Komel, Radovan Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development |
title | Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development |
title_full | Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development |
title_fullStr | Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development |
title_full_unstemmed | Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development |
title_short | Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development |
title_sort | characterization and risk association of polymorphisms in aurora kinases a, b and c with genetic susceptibility to gastric cancer development |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744709/ https://www.ncbi.nlm.nih.gov/pubmed/31521144 http://dx.doi.org/10.1186/s12885-019-6133-z |
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