Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer

Mia M. Gaudet; Tomas Kirchhoff; Todd Green; Joseph Vijai; Joshua M. Korn; Candace Guiducci; Ayellet V. Segre; Kate McGee; Lesley McGuffog; Christiana Kartsonaki; Jonathan Morrison; Sue Healey; Olga M. Sinilnikova; Dominique Stoppa-Lyonnet; Sylvie Mazoyer; Marion Gauthier-Villars; Hagay Sobol; Michel Longy; Marc Frenay; Frans B. L. Hogervorst; Matti A. Rookus; Margriet J. Collee; Nicoline Hoogerbrugge; Kees E. P. van Roozendaal; Marion Piedmonte; Wendy S. Rubinstein; Stacy R. Nerenstone; Linda Van Le; Stephanie V. Blank; Trinidad Caldes; Miguel De La Hoya; Heli Nevanlinna; Kristiina Aittomaki; Conxi Lazaro; Ignacio Blanco; Adalgeir Arason; Oskar T. Johannsson; Rosa B. Barkardottir; Peter Devilee; Olofunmilayo I. Olopade; Susan L. Neuhausen; Xianshu Wang; Zachary S. Fredericksen; Paolo Peterlongo; Siranoush Manoukian; Monica Barile; Alessandra Viel; Paolo Radice; Catherine M. Phelan; Steven A. Narod; Gad Rennert; Flavio Lejbkowicz; Anath Flugelman; Irene L. Andrulis; Gord Glendon; Hilmi Ozcelik; Amanda E. Toland; Marco Montagna; Emma D'Andrea; Eitan Friedman; Yael Laitman; Ake Borg; Mary S. Beattie; Susan J. Ramus; Susan M. Domchek; Katherine L. Nathanson; Tim Rebbeck; Amanda B. Spurdle; Xiaoqing Chen; Helene Holland; Esther M. John; John L. Hopper; Saundra Buys; Mary B. Daly; Melissa C. Southey; Mary Beth Terry; Nadine Tung; Thomas van Overeem Hansen; Finn C. Nielsen; Mark I. Greene; Phuong L. Mai; Ana Osorio; Mercedes Duran; Raquel Andres Conejero; Javier Benitez; Jeffrey N. Weitzel; Judy Garber; Ute Hamann; Susan Peock; Margaret Cook; Clare Oliver; Debra Frost; Radka Platte; D. Gareth Evans; Fiona Lalloo; Ros Eeles; Louise Izatt; Lisa Walker; Jacqueline Eason; Julian Barwell; Andrew K. Godwin; Rita K. Schmutzler; Barbara Wappenschmidt; Stefanie Engert; Norbert Arnold; Dorothea Gadzicki; Michael Dean; Bert Gold; Robert J. Klein; Fergus J. Couch; Georgia Chenevix-Trench; Douglas F. Easton; Mark J. Daly; Antonis C. Antoniou; David M. Altshuler; Encarna Gomez Garcia; Kenneth Offit

doi:10.1371/journal.pgen.1001183

Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer

Mia M. Gaudet^*, Tomas Kirchhoff, Todd Green, Joseph Vijai, Joshua M. Korn, Candace Guiducci, Ayellet V. Segre, Kate McGee, Lesley McGuffog, Christiana Kartsonaki, Jonathan Morrison, Sue Healey, Olga M. Sinilnikova, Dominique Stoppa-Lyonnet, Sylvie Mazoyer, Marion Gauthier-Villars, Hagay Sobol, Michel Longy, Marc Frenay, Frans B. L. HogervorstMatti A. Rookus, Margriet J. Collee, Nicoline Hoogerbrugge, Kees E. P. van Roozendaal, Marion Piedmonte, Wendy S. Rubinstein, Stacy R. Nerenstone, Linda Van Le, Stephanie V. Blank, Trinidad Caldes, Miguel De La Hoya, Heli Nevanlinna, Kristiina Aittomaki, Conxi Lazaro, Ignacio Blanco, Adalgeir Arason, Oskar T. Johannsson, Rosa B. Barkardottir, Peter Devilee, Olofunmilayo I. Olopade, Susan L. Neuhausen, Xianshu Wang, Zachary S. Fredericksen, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, Alessandra Viel, Paolo Radice, Catherine M. Phelan, Steven A. Narod, Gad Rennert, Flavio Lejbkowicz, Anath Flugelman, Irene L. Andrulis, Gord Glendon, Hilmi Ozcelik, Amanda E. Toland, Marco Montagna, Emma D'Andrea, Eitan Friedman, Yael Laitman, Ake Borg, Mary S. Beattie, Susan J. Ramus, Susan M. Domchek, Katherine L. Nathanson, Tim Rebbeck, Amanda B. Spurdle, Xiaoqing Chen, Helene Holland, Esther M. John, John L. Hopper, Saundra Buys, Mary B. Daly, Melissa C. Southey, Mary Beth Terry, Nadine Tung, Thomas van Overeem Hansen, Finn C. Nielsen, Mark I. Greene, Phuong L. Mai, Ana Osorio, Mercedes Duran, Raquel Andres Conejero, Javier Benitez, Jeffrey N. Weitzel, Judy Garber, Ute Hamann, Susan Peock, Margaret Cook, Clare Oliver, Debra Frost, Radka Platte, D. Gareth Evans, Fiona Lalloo, Ros Eeles, Louise Izatt, Lisa Walker, Jacqueline Eason, Julian Barwell, Andrew K. Godwin, Rita K. Schmutzler, Barbara Wappenschmidt, Stefanie Engert, Norbert Arnold, Dorothea Gadzicki, Michael Dean, Bert Gold, Robert J. Klein, Fergus J. Couch, Georgia Chenevix-Trench, Douglas F. Easton, Mark J. Daly, Antonis C. Antoniou, David M. Altshuler, Encarna Gomez Garcia, Kenneth Offit

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (

Original language	English
Article number	1001183
Journal	Plos Genetics
Volume	6
Issue number	10
DOIs	https://doi.org/10.1371/journal.pgen.1001183
Publication status	Published - Oct 2010

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10.1371/journal.pgen.1001183Licence: CC BY

Cite this

Gaudet, M. M., Kirchhoff, T., Green, T., Vijai, J., Korn, J. M., Guiducci, C., Segre, A. V., McGee, K., McGuffog, L., Kartsonaki, C., Morrison, J., Healey, S., Sinilnikova, O. M., Stoppa-Lyonnet, D., Mazoyer, S., Gauthier-Villars, M., Sobol, H., Longy, M., Frenay, M., ... Offit, K. (2010). Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer. Plos Genetics, 6(10), Article 1001183. https://doi.org/10.1371/journal.pgen.1001183

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abstract = "The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (",

author = "Gaudet, {Mia M.} and Tomas Kirchhoff and Todd Green and Joseph Vijai and Korn, {Joshua M.} and Candace Guiducci and Segre, {Ayellet V.} and Kate McGee and Lesley McGuffog and Christiana Kartsonaki and Jonathan Morrison and Sue Healey and Sinilnikova, {Olga M.} and Dominique Stoppa-Lyonnet and Sylvie Mazoyer and Marion Gauthier-Villars and Hagay Sobol and Michel Longy and Marc Frenay and Hogervorst, {Frans B. L.} and Rookus, {Matti A.} and Collee, {Margriet J.} and Nicoline Hoogerbrugge and {van Roozendaal}, {Kees E. P.} and Marion Piedmonte and Rubinstein, {Wendy S.} and Nerenstone, {Stacy R.} and {Van Le}, Linda and Blank, {Stephanie V.} and Trinidad Caldes and {De La Hoya}, Miguel and Heli Nevanlinna and Kristiina Aittomaki and Conxi Lazaro and Ignacio Blanco and Adalgeir Arason and Johannsson, {Oskar T.} and Barkardottir, {Rosa B.} and Peter Devilee and Olopade, {Olofunmilayo I.} and Neuhausen, {Susan L.} and Xianshu Wang and Fredericksen, {Zachary S.} and Paolo Peterlongo and Siranoush Manoukian and Monica Barile and Alessandra Viel and Paolo Radice and Phelan, {Catherine M.} and Narod, {Steven A.} and Gad Rennert and Flavio Lejbkowicz and Anath Flugelman and Andrulis, {Irene L.} and Gord Glendon and Hilmi Ozcelik and Toland, {Amanda E.} and Marco Montagna and Emma D'Andrea and Eitan Friedman and Yael Laitman and Ake Borg and Beattie, {Mary S.} and Ramus, {Susan J.} and Domchek, {Susan M.} and Nathanson, {Katherine L.} and Tim Rebbeck and Spurdle, {Amanda B.} and Xiaoqing Chen and Helene Holland and John, {Esther M.} and Hopper, {John L.} and Saundra Buys and Daly, {Mary B.} and Southey, {Melissa C.} and Terry, {Mary Beth} and Nadine Tung and Hansen, {Thomas van Overeem} and Nielsen, {Finn C.} and Greene, {Mark I.} and Mai, {Phuong L.} and Ana Osorio and Mercedes Duran and {Andres Conejero}, Raquel and Javier Benitez and Weitzel, {Jeffrey N.} and Judy Garber and Ute Hamann and Susan Peock and Margaret Cook and Clare Oliver and Debra Frost and Radka Platte and Evans, {D. Gareth} and Fiona Lalloo and Ros Eeles and Louise Izatt and Lisa Walker and Jacqueline Eason and Julian Barwell and Godwin, {Andrew K.} and Schmutzler, {Rita K.} and Barbara Wappenschmidt and Stefanie Engert and Norbert Arnold and Dorothea Gadzicki and Michael Dean and Bert Gold and Klein, {Robert J.} and Couch, {Fergus J.} and Georgia Chenevix-Trench and Easton, {Douglas F.} and Daly, {Mark J.} and Antoniou, {Antonis C.} and Altshuler, {David M.} and {Gomez Garcia}, Encarna and Kenneth Offit",

year = "2010",

month = oct,

doi = "10.1371/journal.pgen.1001183",

language = "English",

volume = "6",

journal = "Plos Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "10",

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Gaudet, MM, Kirchhoff, T, Green, T, Vijai, J, Korn, JM, Guiducci, C, Segre, AV, McGee, K, McGuffog, L, Kartsonaki, C, Morrison, J, Healey, S, Sinilnikova, OM, Stoppa-Lyonnet, D, Mazoyer, S, Gauthier-Villars, M, Sobol, H, Longy, M, Frenay, M, Hogervorst, FBL, Rookus, MA, Collee, MJ, Hoogerbrugge, N, van Roozendaal, KEP, Piedmonte, M, Rubinstein, WS, Nerenstone, SR, Van Le, L, Blank, SV, Caldes, T, De La Hoya, M, Nevanlinna, H, Aittomaki, K, Lazaro, C, Blanco, I, Arason, A, Johannsson, OT, Barkardottir, RB, Devilee, P, Olopade, OI, Neuhausen, SL, Wang, X, Fredericksen, ZS, Peterlongo, P, Manoukian, S, Barile, M, Viel, A, Radice, P, Phelan, CM, Narod, SA, Rennert, G, Lejbkowicz, F, Flugelman, A, Andrulis, IL, Glendon, G, Ozcelik, H, Toland, AE, Montagna, M, D'Andrea, E, Friedman, E, Laitman, Y, Borg, A, Beattie, MS, Ramus, SJ, Domchek, SM, Nathanson, KL, Rebbeck, T, Spurdle, AB, Chen, X, Holland, H, John, EM, Hopper, JL, Buys, S, Daly, MB, Southey, MC, Terry, MB, Tung, N, Hansen, TVO, Nielsen, FC, Greene, MI, Mai, PL, Osorio, A, Duran, M, Andres Conejero, R, Benitez, J, Weitzel, JN, Garber, J, Hamann, U, Peock, S, Cook, M, Oliver, C, Frost, D, Platte, R, Evans, DG, Lalloo, F, Eeles, R, Izatt, L, Walker, L, Eason, J, Barwell, J, Godwin, AK, Schmutzler, RK, Wappenschmidt, B, Engert, S, Arnold, N, Gadzicki, D, Dean, M, Gold, B, Klein, RJ, Couch, FJ, Chenevix-Trench, G, Easton, DF, Daly, MJ, Antoniou, AC, Altshuler, DM, Gomez Garcia, E & Offit, K 2010, 'Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer', Plos Genetics, vol. 6, no. 10, 1001183. https://doi.org/10.1371/journal.pgen.1001183

TY - JOUR

T1 - Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer

AU - Gaudet, Mia M.

AU - Kirchhoff, Tomas

AU - Green, Todd

AU - Vijai, Joseph

AU - Korn, Joshua M.

AU - Guiducci, Candace

AU - Segre, Ayellet V.

AU - McGee, Kate

AU - McGuffog, Lesley

AU - Kartsonaki, Christiana

AU - Morrison, Jonathan

AU - Healey, Sue

AU - Sinilnikova, Olga M.

AU - Stoppa-Lyonnet, Dominique

AU - Mazoyer, Sylvie

AU - Gauthier-Villars, Marion

AU - Sobol, Hagay

AU - Longy, Michel

AU - Frenay, Marc

AU - Hogervorst, Frans B. L.

AU - Rookus, Matti A.

AU - Collee, Margriet J.

AU - Hoogerbrugge, Nicoline

AU - van Roozendaal, Kees E. P.

AU - Piedmonte, Marion

AU - Rubinstein, Wendy S.

AU - Nerenstone, Stacy R.

AU - Van Le, Linda

AU - Blank, Stephanie V.

AU - Caldes, Trinidad

AU - De La Hoya, Miguel

AU - Nevanlinna, Heli

AU - Aittomaki, Kristiina

AU - Lazaro, Conxi

AU - Blanco, Ignacio

AU - Arason, Adalgeir

AU - Johannsson, Oskar T.

AU - Barkardottir, Rosa B.

AU - Devilee, Peter

AU - Olopade, Olofunmilayo I.

AU - Neuhausen, Susan L.

AU - Wang, Xianshu

AU - Fredericksen, Zachary S.

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Barile, Monica

AU - Viel, Alessandra

AU - Radice, Paolo

AU - Phelan, Catherine M.

AU - Narod, Steven A.

AU - Rennert, Gad

AU - Lejbkowicz, Flavio

AU - Flugelman, Anath

AU - Andrulis, Irene L.

AU - Glendon, Gord

AU - Ozcelik, Hilmi

AU - Toland, Amanda E.

AU - Montagna, Marco

AU - D'Andrea, Emma

AU - Friedman, Eitan

AU - Laitman, Yael

AU - Borg, Ake

AU - Beattie, Mary S.

AU - Ramus, Susan J.

AU - Domchek, Susan M.

AU - Nathanson, Katherine L.

AU - Rebbeck, Tim

AU - Spurdle, Amanda B.

AU - Chen, Xiaoqing

AU - Holland, Helene

AU - John, Esther M.

AU - Hopper, John L.

AU - Buys, Saundra

AU - Daly, Mary B.

AU - Southey, Melissa C.

AU - Terry, Mary Beth

AU - Tung, Nadine

AU - Hansen, Thomas van Overeem

AU - Nielsen, Finn C.

AU - Greene, Mark I.

AU - Mai, Phuong L.

AU - Osorio, Ana

AU - Duran, Mercedes

AU - Andres Conejero, Raquel

AU - Benitez, Javier

AU - Weitzel, Jeffrey N.

AU - Garber, Judy

AU - Hamann, Ute

AU - Peock, Susan

AU - Cook, Margaret

AU - Oliver, Clare

AU - Frost, Debra

AU - Platte, Radka

AU - Evans, D. Gareth

AU - Lalloo, Fiona

AU - Eeles, Ros

AU - Izatt, Louise

AU - Walker, Lisa

AU - Eason, Jacqueline

AU - Barwell, Julian

AU - Godwin, Andrew K.

AU - Schmutzler, Rita K.

AU - Wappenschmidt, Barbara

AU - Engert, Stefanie

AU - Arnold, Norbert

AU - Gadzicki, Dorothea

AU - Dean, Michael

AU - Gold, Bert

AU - Klein, Robert J.

AU - Couch, Fergus J.

AU - Chenevix-Trench, Georgia

AU - Easton, Douglas F.

AU - Daly, Mark J.

AU - Antoniou, Antonis C.

AU - Altshuler, David M.

AU - Gomez Garcia, Encarna

AU - Offit, Kenneth

PY - 2010/10

Y1 - 2010/10

N2 - The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (

AB - The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (

U2 - 10.1371/journal.pgen.1001183

DO - 10.1371/journal.pgen.1001183

M3 - Article

C2 - 21060860

SN - 1553-7390

VL - 6

JO - Plos Genetics

JF - Plos Genetics

IS - 10

M1 - 1001183

ER -