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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

Couch, Fergus J.; Sinilnikova, Olga; Vierkant, Robert A.; Pankratz, V. Shane; Fredericksen, Zachary S.; Stoppa-Lyonnet, Dominique; Coupier, Isabelle; Hughes, David; Hardouin, Agnes and Berthet, Pascaline, et al. (2007) In Cancer Epidemiology Biomarkers & Prevention 16(7). p.1416-1421
Abstract
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... (More)
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. (Less)
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Cancer Epidemiology Biomarkers & Prevention
volume
16
issue
7
pages
1416 - 1421
publisher
American Association for Cancer Research
external identifiers
  • wos:000248174800013
  • scopus:34447498739
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-07-0129
language
English
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yes
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f7145c23-ede9-4d6b-ab85-90e71859726f (old id 692809)
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2007-12-06 11:29:19
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2017-01-01 07:10:05
@article{f7145c23-ede9-4d6b-ab85-90e71859726f,
  abstract     = {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.},
  author       = {Couch, Fergus J. and Sinilnikova, Olga and Vierkant, Robert A. and Pankratz, V. Shane and Fredericksen, Zachary S. and Stoppa-Lyonnet, Dominique and Coupier, Isabelle and Hughes, David and Hardouin, Agnes and Berthet, Pascaline and Peock, Susan and Cook, Margaret and Baynes, Caroline and Hodgson, Shirley and Morrison, Patrick J. and Porteous, Mary E. and Jakubowska, Anna and Lubinski, Jan and Gronwald, Jacek and Spurdle, Amanda B. and kConFab, [unknown] and Schmutzler, Rita and Versmold, Beatrix and Engel, Christoph and Meindl, Alfons and Sutter, Christian and Horst, Jurgen and Schaefer, Dieter and Offit, Kenneth and Kirchhoff, Tomas and Andrulis, Irene L. and Ilyushik, Eduard and Glendon, Gordon and Devilee, Peter and Vreeswijk, Maaike P. G. and Vasen, Hans F. A. and Borg, Åke and Harbst, Katja and Struewing, Jeffery P. and Greene, Mark H. and Neuhausen, Susan L. and Rebbeck, Timothy R. and Nathanson, Katherine and Domchek, Susan and Wagner, Theresa and Garber, Judy E. and Szabo, Csilla and Zikan, Michal and Foretova, Lenka and Olson, Janet E. and Sellers, Thomas A. and Lindor, Noralane and Ll, Heli Nevanlinna and Tommiska, Johanna and Aittomaki, Kristiina and Hamann, Ute and Rashid, Muhammad U. and Torres, Diana and Simard, Jacques and Durocher, Francine and Guenard, Frederic and Lynch, Henry T. and Isaacs, Claudine and Weitzel, Jeffrey and Olopade, Olufunmilayo I. and Narod, Steven and Daly, Mary B. and Godwin, Andrew K. and Tomlinson, Gail and Easton, Douglas F. and Chenevix-Trench, Georgia and Antoniou, Antonis C.},
  issn         = {1538-7755},
  language     = {eng},
  number       = {7},
  pages        = {1416--1421},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A consortium of investigators of modifiers of BRCA1/2 study},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-07-0129},
  volume       = {16},
  year         = {2007},
}