Functional polymorphism 57Val>Ile of aurora kinase A associated with increased risk of gastric cancer progression.
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.
Ju
Hyoungseok
H
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
Cho
Hyunmi
H
Kim
Yong Sung
YS
Kim
Woo Ho
WH
Ihm
Chunhwa
C
Noh
Seung-Moo
SM
Kim
Jin-Bok
JB
Hahn
Dong-Soo
DS
Choi
Bo-Yuol
BY
Kang
Changwon
C
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*
D007532:Isoleucine; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D014633:Valine