title: Functional polymorphism 57Val>Ile of aurora kinase A associated with increased risk of gastric cancer progression.
abstract: Overexpression or amplification of the aurora kinase A (AURKA) gene induces chromosomal instability and transformation. AURKA SNPs are associated with several human cancers but their association with gastric cancer has yet to be investigated. In this study, 501 gastric cancer patients and 427 controls were genotyped for two coding SNPs in AURKA, 91A>T (31Ile>Phe) and 169G>A (57Val>Ile). Allele or genotype association with gastric cancer susceptibility was not observed in comparisons between the patient and control samples. However, 169G/G genotype was significantly more frequent in advanced gastric cancers than in early gastric cancers (age/sex-adjusted OR=2.2, 95% CI=1.3-3.8, P=0.0042). Moreover, the elevated risk of gastric cancer progression was associated with 91T-169G (age/sex-adjusted OR=1.9, 95% CI=1.1-3.4, P=0.025) and 91A-169G (age/sex-adjusted OR=1.6, 95% CI=1.0-2.6, P=0.048) haplotypes, having approximately 2.5-fold higher kinase activity than 91T-169A haplotype. The results suggest that 169G>A in AURKA is associated with progression of gastric cancer by affecting relative kinase activities of AURKA variants.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
authors.forename: Hyoungseok
authors.initials: H
authors.lastname: Ju
authors.forename: Hyunmi
authors.initials: H
authors.lastname: Cho
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Chunhwa
authors.initials: C
authors.lastname: Ihm
authors.forename: Seung-Moo
authors.initials: SM
authors.lastname: Noh
authors.forename: Jin-Bok
authors.initials: JB
authors.lastname: Kim
authors.forename: Dong-Soo
authors.initials: DS
authors.lastname: Hahn
authors.forename: Bo-Yuol
authors.initials: BY
authors.lastname: Choi
authors.forename: Changwon
authors.initials: C
authors.lastname: Kang
mesh_terms: D000483:Alleles; D064096:Aurora Kinase A; D064127:Aurora Kinases; D016022:Case-Control Studies; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007532:Isoleucine / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D012306:Risk; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D014633:Valine / Q000235:genetics*
chemical_list: D007532:Isoleucine; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D014633:Valine