Genetic variations in AURORA cell cycle kinases are associated with glioblastoma multiforme

Sci Rep. 2021 Aug 31;11(1):17444. doi: 10.1038/s41598-021-96935-y.

Abstract

Glioblastoma multiforme (GBM) is the most frequent type of primary astrocytomas. We examined the association between single nucleotide polymorphisms (SNPs) in Aurora kinase A (AURKA), Aurora kinase B (AURKB), Aurora kinase C (AURKC) and Polo-like kinase 1 (PLK1) mitotic checkpoint genes and GBM risk by qPCR genotyping. In silico analysis was performed to evaluate effects of polymorphic biological sequences on protein binding motifs. Chi-square and Fisher statistics revealed a significant difference in genotypes frequencies between GBM patients and controls for AURKB rs2289590 variant (p = 0.038). Association with decreased GBM risk was demonstrated for AURKB rs2289590 AC genotype (OR = 0.54; 95% CI = 0.33-0.88; p = 0.015). Furthermore, AURKC rs11084490 CG genotype was associated with lower GBM risk (OR = 0.57; 95% CI = 0.34-0.95; p = 0.031). Bioinformatic analysis of rs2289590 polymorphic region identified additional binding site for the Yin-Yang 1 (YY1) transcription factor in the presence of C allele. Our results indicated that rs2289590 in AURKB and rs11084490 in AURKC were associated with a reduced GBM risk. The present study was performed on a less numerous but ethnically homogeneous population. Hence, future investigations in larger and multiethnic groups are needed to strengthen these results.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aurora Kinase A / genetics*
  • Aurora Kinase B / genetics*
  • Aurora Kinase C / genetics*
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Cell Cycle Proteins / genetics*
  • Female
  • Follow-Up Studies
  • Genotype
  • Glioblastoma / genetics
  • Glioblastoma / pathology*
  • Humans
  • M Phase Cell Cycle Checkpoints
  • Male
  • Middle Aged
  • Polo-Like Kinase 1
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Proto-Oncogene Proteins
  • AURKA protein, human
  • AURKB protein, human
  • AURKC protein, human
  • Aurora Kinase A
  • Aurora Kinase B
  • Aurora Kinase C
  • Protein Serine-Threonine Kinases