Aurora-A/STK15 T+91A is a general low penetrance cancer susceptibility gene: a meta-analysis of multiple cancer types.
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.
Ewart-Toland
Amanda
A
UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
Dai
Qi
Q
Gao
Yu-Tang
YT
Nagase
Hiroki
H
Dunlop
Malcolm G
MG
Farrington
Susan M
SM
Barnetson
Rebecca A
RA
Anton-Culver
Hoda
H
Peel
David
D
Ziogas
Argyrios
A
Lin
Dongxin
D
Miao
Xiaoping
X
Sun
Tong
T
Ostrander
Elaine A
EA
Stanford
Janet L
JL
Langlois
Mariela
M
Chan
June M
JM
Yuan
Jinwei
J
Harris
Curtis C
CC
Bowman
Elise D
ED
Clayman
Gary L
GL
Lippman
Scott M
SM
Lee
J Jack
JJ
Zheng
Wei
W
Balmain
Allan
A
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
C576917:AURKA protein, human; C576918:Aurka protein, mouse; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases