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

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.

Mutational Spectrum of LDLR and PCSK9 Genes Identified in Iranian Patients With Premature Coronary Artery Disease and Familial Hypercholesterolemia

“…Accordingly, the absence of mutations in the FH-mutation–negative probands in our study may be attributable to nucleotide alterations in other genes, nucleotide variations in other parts of the APOB gene (not addressed in this study), or a combination of LDL-C-raising alleles. Be that as it may, previous studies on other diseases have demonstrated that the presence and combinations of some polymorphisms can render individuals more susceptible to disease ( Khajali and Khajali, 2014 ; Mesic et al, 2019 ; Pinheiro et al, 2019 ).…”

The impact of Aurora kinase A genetic polymorphisms on cervical cancer progression and clinicopathologic characteristics

“…Ishikawa et al found that an allele T in AURKA SNP rs2273535 and T in rs1047972 were correlated with a reduced early adverse reaction in cervical cancer patients who received pelvic radiotherapy, but this has nothing to do with the cancer itself 41 . In addition, Mesic et al suggested that AURKA rs1047922 polymorphisms may influence the development of gastric cancer 42 . Although AURKA SNP rs758099 is located in intron area, they also found that it could have an impact on gastric cancer development.…”

AURKA gene polymorphisms and central nervous system tumor susceptibility in Chinese children

“…In our study, although, AURKA rs1047972 revealed negative results for altering CNS tumor risk, AURKA rs1047972 variants were identified to change lung adenocarcinoma (LADC) development probably [ 47 ]. Moreover, the rs1047972 variants were associated with elevated gastric cancer (GC) risk and basal-like breast cancer [ 48 , 49 ]. With no association of AURKA rs2273535 with CNS tumor susceptibility, AURKA rs2273535 polymorphisms were associated with overall enhanced cancer susceptibility, particularly breast cancer [ 50 ].…”