Association of theAURKAandAURKCgene polymorphisms with an increased risk of gastric cancer

Abstract

Single nucleotide polymorphisms (SNPs) in mitotic checkpoint genes can contribute to susceptibility of human cancer, including gastric cancer (GC). We aimed to investigate the effects of Aurora kinase A (AURKA), Aurora kinase B (AURKB), and Aurora kinase C (AURKC) gene polymorphisms on GC risk in Slovenian population. We genotyped four SNPs in AURKA (rs2273535 and rs1047972), AURKB (rs2241909), and AURKC (rs758099) in a total of 128 GC patients and 372 healthy controls using TaqMan allelic discrimination assays to evaluate their effects on GC risk. Our results showed that genotype frequencies between cases and controls were significantly different for rs1047972 and rs758099 (P < 0.05). Our study demonstrated that AURKA rs1047972 TT and (CC 1 CT) genotypes were significantly associated with an increased risk of gastric cancer. Our results additionally revealed that AURKC rs758099 TT and (CC 1 CT) genotypes were also associated with increased GC risk. In stratified analysis, genotypes TT and (CC 1 CT) of AURKA rs1047972 SNP were associated with increased risk of both, intestinal and diffuse, types of GC. In addition, AURKC rs758099 TT and (CC 1 CT) genotypes were positively associated with increased intestinal type GC risk, but not with an increased diffuse type GC risk. Based on these results, we can conclude that AURKA rs1047972 and AURKC rs758099 polymorphisms could affect the risk of GC development. Further larger studies are needed to confirm these findings. V C 2016 IUBMB Life, 68(8): [634][635][636][637][638][639][640][641][642][643][644] 2016

Single nucleotide polymorphisms rs911160 in AURKA and rs2289590 in AURKB mitotic checkpoint genes contribute to gastric cancer susceptibility

“…Analysis of AURKA haplotypes demonstrated that the frequency of G rs911160 ‐C rs1047972 ‐T rs2273535 haplotype was significantly higher in patients when compared to the control group, highlighting significant effects of this haplotype on increased risk of stomach cancer development. These findings confirmed the results obtained by individual analysis of polymorphisms in AURKA mitotic gene [Mesic et al, ]. In silico analysis of rs911160 revealed that in the presence of the minor C allele, additional NF‐Y, NF‐1 and NFI‐CTF binding motifs were recognized.…”

“…These variants were associated with reduced risk for the development of diffuse type, increased survival, and decreased probability for the development of poorly differentiated adenocarcinoma [Bao et al, 2016]. Two previous studies also revealed significant associations between genotypes of rs758099 in mitotic kinase AURKC and rs151658 in mitotic kinase TTK and histopathological variables of patients, including Lauren classification and the degree of differentiation Mesic et al, 2016]. Analysis of AURKA haplotypes demonstrated that the frequency of G rs911160 -C rs1047972 -T rs2273535 haplotype was significantly higher in patients when compared to the control group, highlighting significant effects of this haplotype on increased risk of stomach cancer development.…”

“…To perform haplotype analysis for polymorphisms in AURKA gene, we extracted raw genotyping data for rs1047972 and rs2273535 SNPs, from our previous study [Mesic et al, ] and combined them with the genotyping data set for rs911160 and rs8173 from the present study. Using Haploview software, single haplotype block was created that included SNPs, rs911160, rs1047972, and rs2273535, having an average Lewontin's D′ > 0.8 (D′ = 1.0 value demonstrates the strongest linkage disequilibrium between two given polymorphisms) (Fig.…”

“…These variants were associated with reduced risk for the development of diffuse type, increased survival, and decreased probability for the development of poorly differentiated adenocarcinoma [Bao et al, ]. Two previous studies also revealed significant associations between genotypes of rs758099 in mitotic kinase AURKC and rs151658 in mitotic kinase TTK and histopathological variables of patients, including Lauren classification and the degree of differentiation [Hudler et al, ; Mesic et al, ].…”

Screening for the Homozygous C.144DELC Mutation in Aurkc Gene in Algerian Infertile Men

“…Aurora kinase family is comprised regulators controlling chromosome segregation and condensation, centrosome duplication, G2/M transition, kinetochore attachment, and cytokinesis [12]. Three types of Aurora kinases are present in mammalian cells, AURKA, AURKB, and AURKC which have specific subcellular localizations and functions during the cell cycle.…”