title: Aurora-A/STK15 T+91A is a general low penetrance cancer susceptibility gene: a meta-analysis of multiple cancer types.
abstract: STK15 (Aurora-A) is a serine/threonine kinase involved in mitotic chromosomal segregation. A genetic variant in STK15 T+91A (resulting in the amino acid substitution F31I) is associated with increased aneuploidy in colon tumors and cell transformation in vitro. Since this polymorphism plays a role in mitotic control-a process critical for all cancer types-we conducted association analyses for risk of cancer development of the colon, breast, prostate, skin, lung and esophagus in 10 independent case-control populations. We carried out a meta-analysis of these 10 case-control studies together with 5 additional published studies for a total of 9549 cases of breast, colon, ovarian, prostate, lung, esophageal and non-melanoma skin cancer and 8326 population or hospital-based controls. Meta-analysis of three colorectal cancer studies showed an increased risk in T+91A homozygotes (OR=1.50; 95% CI of 1.14-1.99). Meta-analysis of four breast cancer studies showed increased risk for T+91A homozygotes (OR=1.35, 95% CI of 1.12-1.64). The results of the multiple cancer type meta-analysis for all 15 studies combined were significant for cancer risk in both homozygotes and heterozygotes. The T+91A heterozygotes show an OR of 1.10 (95% CI of 1.03-1.18, P-value=0.006) and the T+91A homozygotes show an OR of 1.40 (95% CI of 1.22-1.59, P-value<0.001) for cancer risk. These results confirm that the STK15 T+91A variant is a low penetrance cancer susceptibility allele affecting multiple cancer types, and provide genetic evidence from large-scale human population studies that genetic stability at the chromosome level is an important determinant of cancer susceptibility. The data also underline the advantages of comparative association studies involving study populations from different ethnic groups for determination of disease risk.
authors.affiliation: UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
authors.forename: Amanda
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authors.lastname: Ewart-Toland
authors.forename: Qi
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authors.lastname: Dai
authors.forename: Yu-Tang
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authors.lastname: Gao
authors.forename: Hiroki
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authors.lastname: Nagase
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authors.initials: MG
authors.lastname: Dunlop
authors.forename: Susan M
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authors.lastname: Farrington
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authors.initials: RA
authors.lastname: Barnetson
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authors.lastname: Anton-Culver
authors.forename: David
authors.initials: D
authors.lastname: Peel
authors.forename: Argyrios
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authors.lastname: Ziogas
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Tong
authors.initials: T
authors.lastname: Sun
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
authors.forename: Mariela
authors.initials: M
authors.lastname: Langlois
authors.forename: June M
authors.initials: JM
authors.lastname: Chan
authors.forename: Jinwei
authors.initials: J
authors.lastname: Yuan
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
authors.forename: Elise D
authors.initials: ED
authors.lastname: Bowman
authors.forename: Gary L
authors.initials: GL
authors.lastname: Clayman
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Wei
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mesh_terms: D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D001943:Breast Neoplasms / Q000235:genetics; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics
chemical_list: C576917:AURKA protein, human; C576918:Aurka protein, mouse; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases