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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

Author:
  • Fergus J. Couch
  • Olga Sinilnikova
  • Robert A. Vierkant
  • V. Shane Pankratz
  • Zachary S. Fredericksen
  • Dominique Stoppa-Lyonnet
  • Isabelle Coupier
  • David Hughes
  • Agnes Hardouin
  • Pascaline Berthet
  • Susan Peock
  • Margaret Cook
  • Caroline Baynes
  • Shirley Hodgson
  • Patrick J. Morrison
  • Mary E. Porteous
  • Anna Jakubowska
  • Jan Lubinski
  • Jacek Gronwald
  • Amanda B. Spurdle
  • [unknown] kConFab
  • Rita Schmutzler
  • Beatrix Versmold
  • Christoph Engel
  • Alfons Meindl
  • Christian Sutter
  • Jurgen Horst
  • Dieter Schaefer
  • Kenneth Offit
  • Tomas Kirchhoff
  • Irene L. Andrulis
  • Eduard Ilyushik
  • Gordon Glendon
  • Peter Devilee
  • Maaike P. G. Vreeswijk
  • Hans F. A. Vasen
  • Åke Borg
  • Katja Harbst
  • Jeffery P. Struewing
  • Mark H. Greene
  • Susan L. Neuhausen
  • Timothy R. Rebbeck
  • Katherine Nathanson
  • Susan Domchek
  • Theresa Wagner
  • Judy E. Garber
  • Csilla Szabo
  • Michal Zikan
  • Lenka Foretova
  • Janet E. Olson
  • Thomas A. Sellers
  • Noralane Lindor
  • Heli Nevanlinna Ll
  • Johanna Tommiska
  • Kristiina Aittomaki
  • Ute Hamann
  • Muhammad U. Rashid
  • Diana Torres
  • Jacques Simard
  • Francine Durocher
  • Frederic Guenard
  • Henry T. Lynch
  • Claudine Isaacs
  • Jeffrey Weitzel
  • Olufunmilayo I. Olopade
  • Steven Narod
  • Mary B. Daly
  • Andrew K. Godwin
  • Gail Tomlinson
  • Douglas F. Easton
  • Georgia Chenevix-Trench
  • Antonis C. Antoniou
Publishing year: 2007
Language: English
Pages: 1416-1421
Publication/Series: Cancer Epidemiology Biomarkers & Prevention
Volume: 16
Issue: 7
Document type: Journal article
Publisher: American Association for Cancer Research

Abstract english

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 311 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), 0.77-1.061. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% Cl, 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.

Keywords

  • Cancer and Oncology

Other

Published
  • ISSN: 1538-7755
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90