极光激酶 A、B 和 C 多态性的特征及与胃癌发病遗传易感性的关联。

Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development.

机构信息

Department of Biology, Faculty of Science, University of Sarajevo, Zmaja od Bosne 33-35, 71000, Sarajevo, Bosnia and Herzegovina.

Faculty of Medicine, Institute of Biochemistry, Medical Centre for Molecular Biology, University of Ljubljana, Vrazov trg 2, SI-1000, Ljubljana, Slovenia.

出版信息

BMC Cancer. 2019 Sep 14;19(1):919. doi: 10.1186/s12885-019-6133-z.

DOI:10.1186/s12885-019-6133-z

PMID:31521144

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6744709/

Abstract

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.

摘要

背景

编码有丝分裂激酶的基因中的单核苷酸多态性（SNPs）可能会影响胃癌（GC）的发展和进展。

方法

使用 qPCR 对有丝分裂基因中的 9 个 SNPs 进行病例对照研究。该研究包括 116 名 GC 患者和 203 名对照。进行了计算机分析，以评估多态性对转录因子结合位点的影响。

结果

AURKA rs1047972 基因型（CT 与 CC：比值比，1.96；95%置信区间，1.05-3.65；p=0.033；CC+TT 与 CT：比值比，1.94；95%置信区间，1.04-3.60；p=0.036）和 rs911160（CC 与 GG：比值比，5.56；95%置信区间，1.24-24.81；p=0.025；GG+CG 与 CC：比值比，5.26；95%置信区间，1.19-23.22；p=0.028）与 GC 风险增加相关，而某些 rs8173 基因型（CG 与 CC：比值比，0.60；95%置信区间，0.36-0.99；p=0.049；GG 与 CC：比值比，0.38；95%置信区间，0.18-0.79；p=0.010；CC+CG 与 GG：比值比，0.49；95%置信区间，0.25-0.98；p=0.043）具有保护作用。AURKB rs2241909（GG+AG 与 AA：比值比，1.61；95%置信区间，1.01-2.56；p=0.041）和 rs2289590（AC 与 AA：比值比，2.41；95%置信区间，1.47-3.98；p=0.001；CC 与 AA：比值比，6.77；95%置信区间，2.24-20.47；p=0.001；AA+AC 与 CC：比值比，4.23；95%置信区间，1.44-12.40；p=0.009）与 GC 风险增加相关。此外，AURKC rs11084490（GG+CG 与 CC：比值比，1.71；95%置信区间，1.04-2.81；p=0.033）与 GC 风险增加相关。对与 GC 风险增加相关的五个 SNPs 的综合分析检测到所有组合都增加 GC 风险的多态性谱，rs1047972（CT）/rs11084490（CG+GG）的比值比增加 1.51 倍，至 rs1047972（CT）/rs911160（CC）的比值比增加 2.29 倍。rs911160 和 rs2289590 的计算机分析表明，不同的转录因子优先结合于多态性位点，表明 AURKA 和 AURKB 可能根据特定等位基因的存在而受到不同的调控。

结论

我们的结果表明，AURKA（rs1047972 和 rs911160）、AURKB（rs2241909 和 rs2289590）和 AURKC（rs11084490）与 GC 易感性增加相关。我们的研究结果还表明，这些 SNPs 的联合作用可能会影响 GC 风险，这表明联合评估多个多态性的重要性。该研究在数量较少但种族单一的波斯尼亚人群中进行，因此需要进一步在更大的和多民族的群体中进行研究，并评估结果的功能影响，以加强研究结果。