Carcinogenesis Advance Access published online on March 31, 2005
Carcinogenesis, doi:10.1093/carcin/bgi085
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 UCSF Comprehensive Cancer Center, University of California, San Francisco, CA
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 (1). 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 ten 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=.006) and the T+91A homozygotes show an OR of 1.40 (95%CI of 1.22-1.59, p-value <.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.
Received November 17, 2004
Revised February 17, 2005
Accepted March 25, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Aurora-A/STK15 T+91A is a general low penetrance cancer susceptibility gene: a meta-analysis of multiple cancer types
2 Department of Medicine and Vanderbilt-Ingrim Cancer Center, School of Medicine, Vanderbilt University, Nashville TN 37232-8300
3 Department of Epidemiology, Shanghai, Cancer Institute, Shanghai 200032, P.R. China
4 Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY
5 Division of Oncology, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK
6 Epidemiology Division, Department of Medicine, University of California, Irvine, CA
7 Department of Etiology and Carcinogenesis, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
8 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA
9 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA
10 Department of Epidemiology & Biostatistics, University of California, San Francisco, CA; Department of Urology, University of California, San Francisco, CA
11 Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD
12 Department of Head and Neck Surgery and Cancer Biology, M. D. Anderson Cancer Center, Houston, TX
13 Thoracic/Head and Neck Medical Oncology and Clinical Cancer Prevention, M. D. Anderson Cancer Center, Houston, TX
14 Biostatistics, M. D. Anderson Cancer Center, Houston, TX
15 UCSF Comprehensive Cancer Center, University of California, San Francisco, CA; Department of Biochemistry and Biophysics (A.B), University of California San Francisco, San Francisco, CA 94115
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  O. Gautschi, J. Heighway, P. C. Mack, P. R. Purnell, P. N. Lara Jr., and D. R. Gandara Aurora Kinases as Anticancer Drug Targets Clin. Cancer Res., March 15, 2008; 14(6): 1639 - 1648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Carpinelli, R. Ceruti, M. L. Giorgini, P. Cappella, L. Gianellini, V. Croci, A. Degrassi, G. Texido, M. Rocchetti, P. Vianello, et al. PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer Mol. Cancer Ther., December 1, 2007; 6(12): 3158 - 3168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ruiz-Llorente, C. Montero-Conde, R. L. Milne, C. M. Moya, A. Cebrian, R. Leton, A. Cascon, F. Mercadillo, I. Landa, S. Borrego, et al. Association Study of 69 Genes in the Ret Pathway Identifies Low-penetrance Loci in Sporadic Medullary Thyroid Carcinoma Cancer Res., October 1, 2007; 67(19): 9561 - 9567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Yang, T. Ikezoe, C. Nishioka, T. Tasaka, A. Taniguchi, Y. Kuwayama, N. Komatsu, K. Bandobashi, K. Togitani, H. P. Koeffler, et al. AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo Blood, September 15, 2007; 110(6): 2034 - 2040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lassmann, Y. Shen, U. Jutting, P. Wiehle, A. Walch, G. Gitsch, A. Hasenburg, and M. Werner Predictive Value of Aurora-A/STK15 Expression for Late Stage Epithelial Ovarian Cancer Patients Treated by Adjuvant Chemotherapy Clin. Cancer Res., July 15, 2007; 13(14): 4083 - 4091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. N. Landen Jr., Y. G. Lin, A. Immaneni, M. T. Deavers, W. M. Merritt, W. A. Spannuth, D. C. Bodurka, D. M. Gershenson, W. R. Brinkley, and A. K. Sood Overexpression of the Centrosomal Protein Aurora-A Kinase is Associated with Poor Prognosis in Epithelial Ovarian Cancer Patients Clin. Cancer Res., July 15, 2007; 13(14): 4098 - 4104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Couch, O. Sinilnikova, R. A. Vierkant, V. S. Pankratz, Z. S. Fredericksen, D. Stoppa-Lyonnet, I. Coupier, D. Hughes, A. Hardouin, P. Berthet, et al. AURKA F31I Polymorphism and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: A Consortium of Investigators of Modifiers of BRCA1/2 Study Cancer Epidemiol. Biomarkers Prev., July 1, 2007; 16(7): 1416 - 1421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ikezoe, J. Yang, C. Nishioka, T. Tasaka, A. Taniguchi, Y. Kuwayama, N. Komatsu, K. Bandobashi, K. Togitani, H. P. Koeffler, et al. A novel treatment strategy targeting Aurora kinases in acute myelogenous leukemia Mol. Cancer Ther., June 1, 2007; 6(6): 1851 - 1857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, D. Li, C. Wei, S. Sen, A. M. Killary, C. I. Amos, D. B. Evans, J. L. Abbruzzese, and M. L. Frazier Aurora-A and p16 Polymorphisms Contribute to an Earlier Age at Diagnosis of Pancreatic Cancer in Caucasians Clin. Cancer Res., May 15, 2007; 13(10): 3100 - 3104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Perez de Castro, G. de Carcer, and M. Malumbres A census of mitotic cancer genes: new insights into tumor cell biology and cancer therapy Carcinogenesis, May 1, 2007; 28(5): 899 - 912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Briassouli, F. Chan, K. Savage, J. S. Reis-Filho, and S. Linardopoulos Aurora-A Regulation of Nuclear Factor-{kappa}B Signaling by Phosphorylation of I{kappa}B{alpha} Cancer Res., February 15, 2007; 67(4): 1689 - 1695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Gu, Y. Gong, M. Huang, C. Lu, M. R. Spitz, and X. Wu Polymorphisms of STK15 (Aurora-A) gene and lung cancer risk in Caucasians Carcinogenesis, February 1, 2007; 28(2): 350 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Briassouli, F. Chan, and S. Linardopoulos The N-terminal domain of the Aurora-A Phe-31 variant encodes an E3 ubiquitin ligase and mediates ubiquitination of I{kappa}B{alpha} Hum. Mol. Genet., November 15, 2006; 15(22): 3343 - 3350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. A. Ioannidis Common genetic variants for breast cancer: 32 largely refuted candidates and larger prospects. J Natl Cancer Inst, October 4, 2006; 98(19): 1350 - 1353. [Full Text] [PDF]
|
|
|
|
|
|
The Breast Cancer Association Consortium Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium. J Natl Cancer Inst, October 4, 2006; 98(19): 1382 - 1396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Reiter, P. Gais, U. Jutting, M. K. Steuer-Vogt, A. Pickhard, K. Bink, S. Rauser, S. Lassmann, H. Hofler, M. Werner, et al. Aurora Kinase A Messenger RNA Overexpression Is Correlated with Tumor Progression and Shortened Survival in Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., September 1, 2006; 12(17): 5136 - 5141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Fletcher, N. Johnson, C. Palles, I. dos Santos Silva, V. McCormack, J. Whittaker, A. Ashworth, and J. Peto Inconsistent association between the STK15 F31I genetic polymorphism and breast cancer risk. J Natl Cancer Inst, July 19, 2006; 98(14): 1014 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Dahl, G. Kristiansen, K. Gottlob, I. Klaman, E. Ebner, B. Hinzmann, K. Hermann, C. Pilarsky, M. Durst, M. Klinkhammer-Schalke, et al. Molecular Profiling of Laser-Microdissected Matched Tumor and Normal Breast Tissue Identifies Karyopherin {alpha}2 as a Potential Novel Prognostic Marker in Breast Cancer. Clin. Cancer Res., July 1, 2006; 12(13): 3950 - 3960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Han, G. A. Colditz, and D. J. Hunter Lack of associations of selected variants in genes involved in cell cycle and apoptosis with skin cancer risk. Cancer Epidemiol. Biomarkers Prev., March 1, 2006; 15(3): 592 - 593. [Full Text] [PDF]
|
|