AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers

A Consortium of Investigators of Modifiers of BRCA1/2 study

Fergus J. Couch, Olga Sinilnikova, Robert A. Vierkant, V. Shane Pankratz, Zachary S. Fredericksen, Dominique Stoppa-Lyonnet, Isabelle Coupier, David Hughes, Agnès 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 & 52 others Georgia Chenevix-Trench, Amanda Spurdle, 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, Ake Borg, Katja Backenhorn, 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, 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, Antonis C. Antoniou

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1416-1421
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume16
Issue number7
DOIs
StatePublished - Jul 1 2007

Fingerprint

Aurora Kinase A
Research Personnel
Breast Neoplasms
Mutation
Confidence Intervals
Neoplasms
Chromosome Segregation
Ovariectomy
Aneuploidy
Oncogenes
Alleles

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

Cite this

Couch, F. J., Sinilnikova, O., Vierkant, R. A., Pankratz, V. S., Fredericksen, Z. S., Stoppa-Lyonnet, D., ... Antoniou, A. C. (2007). AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A Consortium of Investigators of Modifiers of BRCA1/2 study. Cancer Epidemiology Biomarkers and Prevention, 16(7), 1416-1421. https://doi.org/10.1158/1055-9965.EPI-07-0129

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, Agnès; Berthet, Pascaline; Peock, Susan; Cook, Margaret; Baynes, Caroline; Hodgson, Shirley; Morrison, Patrick J.; Porteous, Mary E.; Jakubowska, Anna; Lubinski, Jan; Gronwald, Jacek; Spurdle, Amanda B.; Chenevix-Trench, Georgia; Spurdle, Amanda; Schmutzler, Rita; Versmold, Beatrix; Engel, Christoph; Meindl, Alfons; Sutter, Christian; Horst, Jurgen; Schaefer, Dieter; Offit, Kenneth; Kirchhoff, Tomas; Andrulis, Irene L.; Ilyushik, Eduard; Glendon, Gordon; Devilee, Peter; Vreeswijk, Maaike P G; Vasen, Hans F A; Borg, Ake; Backenhorn, Katja; Struewing, Jeffery P.; Greene, Mark H.; Neuhausen, Susan L.; Rebbeck, Timothy R.; Nathanson, Katherine; Domchek, Susan; Wagner, Theresa; Garber, Judy E.; Szabo, Csilla; Zikan, Michal; Foretova, Lenka; Olson, Janet E.; Sellers, Thomas A.; Lindor, Noralane; Nevanlinna, Heli; Tommiska, Johanna; Aittomaki, Kristiina; Hamann, Ute; Rashid, Muhammad U.; Torres, Diana; Simard, Jacques; Durocher, Francine; Guenard, Frederic; Lynch, Henry T.; Isaacs, Claudine; Weitzel, Jeffrey; Olopade, Olufunmilayo I.; Narod, Steven; Daly, Mary B.; Godwin, Andrew K.; Tomlinson, Gail; Easton, Douglas F.; Antoniou, Antonis C.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 16, No. 7, 01.07.2007, p. 1416-1421.

Research output: Contribution to journalArticle

Couch, FJ, Sinilnikova, O, Vierkant, RA, Pankratz, VS, Fredericksen, ZS, Stoppa-Lyonnet, D, Coupier, I, Hughes, D, Hardouin, A, Berthet, P, Peock, S, Cook, M, Baynes, C, Hodgson, S, Morrison, PJ, Porteous, ME, Jakubowska, A, Lubinski, J, Gronwald, J, Spurdle, AB, Chenevix-Trench, G, Spurdle, A, Schmutzler, R, Versmold, B, Engel, C, Meindl, A, Sutter, C, Horst, J, Schaefer, D, Offit, K, Kirchhoff, T, Andrulis, IL, Ilyushik, E, Glendon, G, Devilee, P, Vreeswijk, MPG, Vasen, HFA, Borg, A, Backenhorn, K, Struewing, JP, Greene, MH, Neuhausen, SL, Rebbeck, TR, Nathanson, K, Domchek, S, Wagner, T, Garber, JE, Szabo, C, Zikan, M, Foretova, L, Olson, JE, Sellers, TA, Lindor, N, Nevanlinna, H, Tommiska, J, Aittomaki, K, Hamann, U, Rashid, MU, Torres, D, Simard, J, Durocher, F, Guenard, F, Lynch, HT, Isaacs, C, Weitzel, J, Olopade, OI, Narod, S, Daly, MB, Godwin, AK, Tomlinson, G, Easton, DF & Antoniou, AC 2007, 'AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A Consortium of Investigators of Modifiers of BRCA1/2 study', Cancer Epidemiology Biomarkers and Prevention, vol. 16, no. 7, pp. 1416-1421. https://doi.org/10.1158/1055-9965.EPI-07-0129
Couch, Fergus J. ; Sinilnikova, Olga ; Vierkant, Robert A. ; Pankratz, V. Shane ; Fredericksen, Zachary S. ; Stoppa-Lyonnet, Dominique ; Coupier, Isabelle ; Hughes, David ; Hardouin, Agnès ; Berthet, Pascaline ; Peock, Susan ; Cook, Margaret ; Baynes, Caroline ; Hodgson, Shirley ; Morrison, Patrick J. ; Porteous, Mary E. ; Jakubowska, Anna ; Lubinski, Jan ; Gronwald, Jacek ; Spurdle, Amanda B. ; Chenevix-Trench, Georgia ; Spurdle, Amanda ; Schmutzler, Rita ; Versmold, Beatrix ; Engel, Christoph ; Meindl, Alfons ; Sutter, Christian ; Horst, Jurgen ; Schaefer, Dieter ; Offit, Kenneth ; Kirchhoff, Tomas ; Andrulis, Irene L. ; Ilyushik, Eduard ; Glendon, Gordon ; Devilee, Peter ; Vreeswijk, Maaike P G ; Vasen, Hans F A ; Borg, Ake ; Backenhorn, Katja ; Struewing, Jeffery P. ; Greene, Mark H. ; Neuhausen, Susan L. ; Rebbeck, Timothy R. ; Nathanson, Katherine ; Domchek, Susan ; Wagner, Theresa ; Garber, Judy E. ; Szabo, Csilla ; Zikan, Michal ; Foretova, Lenka ; Olson, Janet E. ; Sellers, Thomas A. ; Lindor, Noralane ; Nevanlinna, Heli ; Tommiska, Johanna ; Aittomaki, Kristiina ; Hamann, Ute ; Rashid, Muhammad U. ; Torres, Diana ; Simard, Jacques ; Durocher, Francine ; Guenard, Frederic ; Lynch, Henry T. ; Isaacs, Claudine ; Weitzel, Jeffrey ; Olopade, Olufunmilayo I. ; Narod, Steven ; Daly, Mary B. ; Godwin, Andrew K. ; Tomlinson, Gail ; Easton, Douglas F. ; Antoniou, Antonis C. / AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers : A Consortium of Investigators of Modifiers of BRCA1/2 study. In: Cancer Epidemiology Biomarkers and Prevention. 2007 ; Vol. 16, No. 7. pp. 1416-1421.
@article{b21322574c4e4e61b7d525720f29d717,
title = "AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A Consortium of Investigators of Modifiers of BRCA1/2 study",
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 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.",
author = "Couch, {Fergus J.} and Olga Sinilnikova and Vierkant, {Robert A.} and Pankratz, {V. Shane} and Fredericksen, {Zachary S.} and Dominique Stoppa-Lyonnet and Isabelle Coupier and David Hughes and Agn{\`e}s Hardouin and Pascaline Berthet and Susan Peock and Margaret Cook and Caroline Baynes and Shirley Hodgson and Morrison, {Patrick J.} and Porteous, {Mary E.} and Anna Jakubowska and Jan Lubinski and Jacek Gronwald and Spurdle, {Amanda B.} and Georgia Chenevix-Trench and Amanda Spurdle and Rita Schmutzler and Beatrix Versmold and Christoph Engel and Alfons Meindl and Christian Sutter and Jurgen Horst and Dieter Schaefer and Kenneth Offit and Tomas Kirchhoff and Andrulis, {Irene L.} and Eduard Ilyushik and Gordon Glendon and Peter Devilee and Vreeswijk, {Maaike P G} and Vasen, {Hans F A} and Ake Borg and Katja Backenhorn and Struewing, {Jeffery P.} and Greene, {Mark H.} and Neuhausen, {Susan L.} and Rebbeck, {Timothy R.} and Katherine Nathanson and Susan Domchek and Theresa Wagner and Garber, {Judy E.} and Csilla Szabo and Michal Zikan and Lenka Foretova and Olson, {Janet E.} and Sellers, {Thomas A.} and Noralane Lindor and Heli Nevanlinna and Johanna Tommiska and Kristiina Aittomaki and Ute Hamann and Rashid, {Muhammad U.} and Diana Torres and Jacques Simard and Francine Durocher and Frederic Guenard and Lynch, {Henry T.} and Claudine Isaacs and Jeffrey Weitzel and Olopade, {Olufunmilayo I.} and Steven Narod and Daly, {Mary B.} and Godwin, {Andrew K.} and Gail Tomlinson and Easton, {Douglas F.} and Antoniou, {Antonis C.}",
year = "2007",
month = "7",
day = "1",
doi = "10.1158/1055-9965.EPI-07-0129",
language = "English",
volume = "16",
pages = "1416--1421",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

TY - JOUR

T1 - AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers

T2 - A Consortium of Investigators of Modifiers of BRCA1/2 study

AU - Couch, Fergus J.

AU - Sinilnikova, Olga

AU - Vierkant, Robert A.

AU - Pankratz, V. Shane

AU - Fredericksen, Zachary S.

AU - Stoppa-Lyonnet, Dominique

AU - Coupier, Isabelle

AU - Hughes, David

AU - Hardouin, Agnès

AU - Berthet, Pascaline

AU - Peock, Susan

AU - Cook, Margaret

AU - Baynes, Caroline

AU - Hodgson, Shirley

AU - Morrison, Patrick J.

AU - Porteous, Mary E.

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Gronwald, Jacek

AU - Spurdle, Amanda B.

AU - Chenevix-Trench, Georgia

AU - Spurdle, Amanda

AU - Schmutzler, Rita

AU - Versmold, Beatrix

AU - Engel, Christoph

AU - Meindl, Alfons

AU - Sutter, Christian

AU - Horst, Jurgen

AU - Schaefer, Dieter

AU - Offit, Kenneth

AU - Kirchhoff, Tomas

AU - Andrulis, Irene L.

AU - Ilyushik, Eduard

AU - Glendon, Gordon

AU - Devilee, Peter

AU - Vreeswijk, Maaike P G

AU - Vasen, Hans F A

AU - Borg, Ake

AU - Backenhorn, Katja

AU - Struewing, Jeffery P.

AU - Greene, Mark H.

AU - Neuhausen, Susan L.

AU - Rebbeck, Timothy R.

AU - Nathanson, Katherine

AU - Domchek, Susan

AU - Wagner, Theresa

AU - Garber, Judy E.

AU - Szabo, Csilla

AU - Zikan, Michal

AU - Foretova, Lenka

AU - Olson, Janet E.

AU - Sellers, Thomas A.

AU - Lindor, Noralane

AU - Nevanlinna, Heli

AU - Tommiska, Johanna

AU - Aittomaki, Kristiina

AU - Hamann, Ute

AU - Rashid, Muhammad U.

AU - Torres, Diana

AU - Simard, Jacques

AU - Durocher, Francine

AU - Guenard, Frederic

AU - Lynch, Henry T.

AU - Isaacs, Claudine

AU - Weitzel, Jeffrey

AU - Olopade, Olufunmilayo I.

AU - Narod, Steven

AU - Daly, Mary B.

AU - Godwin, Andrew K.

AU - Tomlinson, Gail

AU - Easton, Douglas F.

AU - Antoniou, Antonis C.

PY - 2007/7/1

Y1 - 2007/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34447498739&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447498739&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-07-0129

DO - 10.1158/1055-9965.EPI-07-0129

M3 - Article

VL - 16

SP - 1416

EP - 1421

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 7

ER -