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AURKA F31I Polymorphism and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: A Consortium of Investigators of Modifiers of BRCA1/2 Study

¹ Departments of Laboratory Medicine and Pathology, ² Medical Genetics, and ³ Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota; ⁴ Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon-Centre Léon Bérard; ⁵ IARC, Lyon, France; ⁶ Institut National de la Sante et de la Recherche Medicale U509, Service de Génétique Oncologique, Institut Curie, Paris, France; ⁷ Centre François Baclesse, Caen, France; ⁸ Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care and ⁹ Cancer Research UK, Human Cancer Genetics Group, Department of Oncology, University of Cambridge, Cambridge, United Kingdom; ¹⁰ South West Thames Regional Genetics Service, St. Georges Hospital, London, United Kingdom; ¹¹ Northern Ireland Regional Genetics Centre, Cancer Genetics Service, Belfast City Hospital, Belfast, United Kingdom; ¹² South East of Scotland Clinical Genetics Service, Western General Hospital, Edinburgh, United Kingdom; ¹³ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland; ¹⁴ Queensland Institute of Medical Research, Brisbane, Queensland, Australia; ¹⁵ The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; ¹⁶ Division of Molecular Gyneco-Oncology, University of Cologne, Cologne, Germany; ¹⁷ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany; ¹⁸ Department of Gynaecology and Obstetrics, Technical University, Munich, Germany; ¹⁹ Institute of Human Genetics, University of Heidelberg; ²⁰ Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Germany; ²¹ Institute of Human Genetics, University of Muenster, Muenster, Germany; ²² Institute of Human Genetics, University of Frankfurt, Frankfurt, Germany; ²³ Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York; ²⁴ Fred A. Litwin Center for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital; ²⁵ Ontario Cancer Genetics Network, Cancer Care Ontario; ²⁶ Centre for Research in Women's Health, Toronto, Ontario, Canada; ²⁷ Department of Human Genetics, Leiden University Medical Center; ²⁸ The Foundation for the Detection of Hereditary Tumors, Leiden, the Netherlands; ²⁹ Department of Oncology, Lund University Hospital, Lund, Sweden; ³⁰ Clinical Genetics Branch and ³¹ Laboratory of Population Genetics, National Cancer Institute, NIH, Bethesda, Maryland; ³² Division of Epidemiology, Department of Medicine, University of California Irvine, Irvine, California; ³³ Abramson Cancer Center, University of Pennsylvania School of Medicine; ³⁴ Fox Chase Cancer Center, Philadelphia, Pennsylvania; ³⁵ Division of Senology, Medical University of Vienna, Vienna, Austria; ³⁶ Dana-Farber Cancer Institute, Boston, Massachusetts; ³⁷ Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic; ³⁸ Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic; ³⁹ Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; Departments of ⁴⁰ Obstetrics and Gynecology and ⁴¹ Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland; ⁴² Cancer Genomics Laboratory, Oncology and Molecular Endocrinology Research Centre, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Quebec, Canada; ⁴³ Department of Preventive Medicine and Public Health, Creighton University, Omaha, Nebraska; ⁴⁴ Lombardi Cancer Center, Georgetown University, Washington, District of Columbia; ⁴⁵ City of Hope Cancer Center, Duarte, California; ⁴⁶ University of Chicago, Chicago, Illinois; and ⁴⁷ University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

Requests for reprints: Fergus J. Couch, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905. Phone: 507-284-3623; Fax: 507-266-0824. E-mail: Couch.fergus{at}mayo.edu

The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 31I allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.06]. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% CI, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1416–21)

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				S. K. Bodvarsdottir, L. Vidarsdottir, and J. E. Eyfjord AURKA and Breast Cancer in BRCA1/2 Mutation Carriers Cancer Epidemiol. Biomarkers Prev., November 1, 2007; 16(11): 2517 - 2517. [Full Text] [PDF]