Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers

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Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers. / Cox, David G.; Simard, Jacques; Sinnett, Daniel; Hamdi, Yosr; Soucy, Penny; Ouimet, Manon; Barjhoux, Laure; Verny-Pierre, Carole; McGuffog, Lesley; Healey, Sue; Szabo, Csilla; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Thomassen, Mads; Gerdes, Anne-Marie; Caligo, Maria A.; Friedman, Eitan; Laitman, Yael; Kaufman, Bella; Paluch, Shani S.; Borg, Åke; Karlsson, Per; Askmalm, Marie Stenmark; Bustinza, Gisela Barbany; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Benitez, Javier; Hamann, Ute; Rookus, Matti A.; van den Ouweland, Ans M. W.; Ausems, Margreet G. E. M.; Aalfs, Cora M.; van Asperen, Christi J.; Devilee, Peter; Gille, Hans J. J. P.; Peock, Susan; Frost, Debra; Evans, D. Gareth; Eeles, Ros; Izatt, Louise; Adlard, Julian; Paterson, Joan; Eason, Jacqueline; Godwin, Andrew K.; Remon, Marie-Alice; Moncoutier, Virginie; Gauthier-Villars, Marion; Lasset, Christine; Giraud, Sophie; Hardouin, Agnes; Berthet, Pascaline; Sobol, Hagay; Eisinger, Francois; de Paillerets, Brigitte Bressac; Caron, Olivier; Delnatte, Capucine; Goldgar, David; Miron, Alex; Ozcelik, Hilmi; Buys, Saundra; Southey, Melissa C.; Terry, Mary Beth; Singer, Christian F.; Dressler, Anne-Catharina; Tea, Muy-Kheng; Hansen, Thomas V. O.; Johannsson, Oskar; Piedmonte, Marion; Rodriguez, Gustavo C.; Basil, Jack B.; Blank, Stephanie; Toland, Amanda E.; Montagna, Marco; Isaacs, Claudine; Blanco, Ignacio; Gayther, Simon A.; Moysich, Kirsten B.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Gadzicki, Dorothea; Fiebig, Britta; Caldes, Trinidad; Laframboise, Rachel; Nevanlinna, Heli; Chen, Xiaoqing; Beesley, Jonathan; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan C.; Couch, Fergus J.; Wang, Xianshu; Peterlongo, Paolo; Manoukian, Siranoush; Bernard, Loris; Radice, Paolo; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Sinilnikova, Olga M.; Olsson, Håkan.

In: Human Molecular Genetics, Vol. 20, No. 23, 2011, p. 4732-4747.

Research output: Contribution to journalArticle

Harvard

Cox, DG, Simard, J, Sinnett, D, Hamdi, Y, Soucy, P, Ouimet, M, Barjhoux, L, Verny-Pierre, C, McGuffog, L, Healey, S, Szabo, C, Greene, MH, Mai, PL, Andrulis, IL, Thomassen, M, Gerdes, A-M, Caligo, MA, Friedman, E, Laitman, Y, Kaufman, B, Paluch, SS, Borg, Å, Karlsson, P, Askmalm, MS, Bustinza, GB, Nathanson, KL, Domchek, SM, Rebbeck, TR, Benitez, J, Hamann, U, Rookus, MA, van den Ouweland, AMW, Ausems, MGEM, Aalfs, CM, van Asperen, CJ, Devilee, P, Gille, HJJP, Peock, S, Frost, D, Evans, DG, Eeles, R, Izatt, L, Adlard, J, Paterson, J, Eason, J, Godwin, AK, Remon, M-A, Moncoutier, V, Gauthier-Villars, M, Lasset, C, Giraud, S, Hardouin, A, Berthet, P, Sobol, H, Eisinger, F, de Paillerets, BB, Caron, O, Delnatte, C, Goldgar, D, Miron, A, Ozcelik, H, Buys, S, Southey, MC, Terry, MB, Singer, CF, Dressler, A-C, Tea, M-K, Hansen, TVO, Johannsson, O, Piedmonte, M, Rodriguez, GC, Basil, JB, Blank, S, Toland, AE, Montagna, M, Isaacs, C, Blanco, I, Gayther, SA, Moysich, KB, Schmutzler, RK, Wappenschmidt, B, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Niederacher, D, Sutter, C, Gadzicki, D, Fiebig, B, Caldes, T, Laframboise, R, Nevanlinna, H, Chen, X, Beesley, J, Spurdle, AB, Neuhausen, SL, Ding, YC, Couch, FJ, Wang, X, Peterlongo, P, Manoukian, S, Bernard, L, Radice, P, Easton, DF, Chenevix-Trench, G, Antoniou, AC, Stoppa-Lyonnet, D, Mazoyer, S, Sinilnikova, OM & Olsson, H 2011, 'Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers', Human Molecular Genetics, vol. 20, no. 23, pp. 4732-4747. https://doi.org/10.1093/hmg/ddr388

APA

CBE

Cox DG, Simard J, Sinnett D, Hamdi Y, Soucy P, Ouimet M, Barjhoux L, Verny-Pierre C, McGuffog L, Healey S, Szabo C, Greene MH, Mai PL, Andrulis IL, Thomassen M, Gerdes A-M, Caligo MA, Friedman E, Laitman Y, Kaufman B, Paluch SS, Borg Å, Karlsson P, Askmalm MS, Bustinza GB, Nathanson KL, Domchek SM, Rebbeck TR, Benitez J, Hamann U, Rookus MA, van den Ouweland AMW, Ausems MGEM, Aalfs CM, van Asperen CJ, Devilee P, Gille HJJP, Peock S, Frost D, Evans DG, Eeles R, Izatt L, Adlard J, Paterson J, Eason J, Godwin AK, Remon M-A, Moncoutier V, Gauthier-Villars M, Lasset C, Giraud S, Hardouin A, Berthet P, Sobol H, Eisinger F, de Paillerets BB, Caron O, Delnatte C, Goldgar D, Miron A, Ozcelik H, Buys S, Southey MC, Terry MB, Singer CF, Dressler A-C, Tea M-K, Hansen TVO, Johannsson O, Piedmonte M, Rodriguez GC, Basil JB, Blank S, Toland AE, Montagna M, Isaacs C, Blanco I, Gayther SA, Moysich KB, Schmutzler RK, Wappenschmidt B, Engel C, Meindl A, Ditsch N, Arnold N, Niederacher D, Sutter C, Gadzicki D, Fiebig B, Caldes T, Laframboise R, Nevanlinna H, Chen X, Beesley J, Spurdle AB, Neuhausen SL, Ding YC, Couch FJ, Wang X, Peterlongo P, Manoukian S, Bernard L, Radice P, Easton DF, Chenevix-Trench G, Antoniou AC, Stoppa-Lyonnet D, Mazoyer S, Sinilnikova OM, Olsson H. 2011. Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers. Human Molecular Genetics. 20(23):4732-4747. https://doi.org/10.1093/hmg/ddr388

MLA

Vancouver

Author

Cox, David G. ; Simard, Jacques ; Sinnett, Daniel ; Hamdi, Yosr ; Soucy, Penny ; Ouimet, Manon ; Barjhoux, Laure ; Verny-Pierre, Carole ; McGuffog, Lesley ; Healey, Sue ; Szabo, Csilla ; Greene, Mark H. ; Mai, Phuong L. ; Andrulis, Irene L. ; Thomassen, Mads ; Gerdes, Anne-Marie ; Caligo, Maria A. ; Friedman, Eitan ; Laitman, Yael ; Kaufman, Bella ; Paluch, Shani S. ; Borg, Åke ; Karlsson, Per ; Askmalm, Marie Stenmark ; Bustinza, Gisela Barbany ; Nathanson, Katherine L. ; Domchek, Susan M. ; Rebbeck, Timothy R. ; Benitez, Javier ; Hamann, Ute ; Rookus, Matti A. ; van den Ouweland, Ans M. W. ; Ausems, Margreet G. E. M. ; Aalfs, Cora M. ; van Asperen, Christi J. ; Devilee, Peter ; Gille, Hans J. J. P. ; Peock, Susan ; Frost, Debra ; Evans, D. Gareth ; Eeles, Ros ; Izatt, Louise ; Adlard, Julian ; Paterson, Joan ; Eason, Jacqueline ; Godwin, Andrew K. ; Remon, Marie-Alice ; Moncoutier, Virginie ; Gauthier-Villars, Marion ; Lasset, Christine ; Giraud, Sophie ; Hardouin, Agnes ; Berthet, Pascaline ; Sobol, Hagay ; Eisinger, Francois ; de Paillerets, Brigitte Bressac ; Caron, Olivier ; Delnatte, Capucine ; Goldgar, David ; Miron, Alex ; Ozcelik, Hilmi ; Buys, Saundra ; Southey, Melissa C. ; Terry, Mary Beth ; Singer, Christian F. ; Dressler, Anne-Catharina ; Tea, Muy-Kheng ; Hansen, Thomas V. O. ; Johannsson, Oskar ; Piedmonte, Marion ; Rodriguez, Gustavo C. ; Basil, Jack B. ; Blank, Stephanie ; Toland, Amanda E. ; Montagna, Marco ; Isaacs, Claudine ; Blanco, Ignacio ; Gayther, Simon A. ; Moysich, Kirsten B. ; Schmutzler, Rita K. ; Wappenschmidt, Barbara ; Engel, Christoph ; Meindl, Alfons ; Ditsch, Nina ; Arnold, Norbert ; Niederacher, Dieter ; Sutter, Christian ; Gadzicki, Dorothea ; Fiebig, Britta ; Caldes, Trinidad ; Laframboise, Rachel ; Nevanlinna, Heli ; Chen, Xiaoqing ; Beesley, Jonathan ; Spurdle, Amanda B. ; Neuhausen, Susan L. ; Ding, Yuan C. ; Couch, Fergus J. ; Wang, Xianshu ; Peterlongo, Paolo ; Manoukian, Siranoush ; Bernard, Loris ; Radice, Paolo ; Easton, Douglas F. ; Chenevix-Trench, Georgia ; Antoniou, Antonis C. ; Stoppa-Lyonnet, Dominique ; Mazoyer, Sylvie ; Sinilnikova, Olga M. ; Olsson, Håkan. / Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers. In: Human Molecular Genetics. 2011 ; Vol. 20, No. 23. pp. 4732-4747.

RIS

TY - JOUR

T1 - Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers

AU - Cox, David G.

AU - Simard, Jacques

AU - Sinnett, Daniel

AU - Hamdi, Yosr

AU - Soucy, Penny

AU - Ouimet, Manon

AU - Barjhoux, Laure

AU - Verny-Pierre, Carole

AU - McGuffog, Lesley

AU - Healey, Sue

AU - Szabo, Csilla

AU - Greene, Mark H.

AU - Mai, Phuong L.

AU - Andrulis, Irene L.

AU - Thomassen, Mads

AU - Gerdes, Anne-Marie

AU - Caligo, Maria A.

AU - Friedman, Eitan

AU - Laitman, Yael

AU - Kaufman, Bella

AU - Paluch, Shani S.

AU - Borg, Åke

AU - Karlsson, Per

AU - Askmalm, Marie Stenmark

AU - Bustinza, Gisela Barbany

AU - Nathanson, Katherine L.

AU - Domchek, Susan M.

AU - Rebbeck, Timothy R.

AU - Benitez, Javier

AU - Hamann, Ute

AU - Rookus, Matti A.

AU - van den Ouweland, Ans M. W.

AU - Ausems, Margreet G. E. M.

AU - Aalfs, Cora M.

AU - van Asperen, Christi J.

AU - Devilee, Peter

AU - Gille, Hans J. J. P.

AU - Peock, Susan

AU - Frost, Debra

AU - Evans, D. Gareth

AU - Eeles, Ros

AU - Izatt, Louise

AU - Adlard, Julian

AU - Paterson, Joan

AU - Eason, Jacqueline

AU - Godwin, Andrew K.

AU - Remon, Marie-Alice

AU - Moncoutier, Virginie

AU - Gauthier-Villars, Marion

AU - Lasset, Christine

AU - Giraud, Sophie

AU - Hardouin, Agnes

AU - Berthet, Pascaline

AU - Sobol, Hagay

AU - Eisinger, Francois

AU - de Paillerets, Brigitte Bressac

AU - Caron, Olivier

AU - Delnatte, Capucine

AU - Goldgar, David

AU - Miron, Alex

AU - Ozcelik, Hilmi

AU - Buys, Saundra

AU - Southey, Melissa C.

AU - Terry, Mary Beth

AU - Singer, Christian F.

AU - Dressler, Anne-Catharina

AU - Tea, Muy-Kheng

AU - Hansen, Thomas V. O.

AU - Johannsson, Oskar

AU - Piedmonte, Marion

AU - Rodriguez, Gustavo C.

AU - Basil, Jack B.

AU - Blank, Stephanie

AU - Toland, Amanda E.

AU - Montagna, Marco

AU - Isaacs, Claudine

AU - Blanco, Ignacio

AU - Gayther, Simon A.

AU - Moysich, Kirsten B.

AU - Schmutzler, Rita K.

AU - Wappenschmidt, Barbara

AU - Engel, Christoph

AU - Meindl, Alfons

AU - Ditsch, Nina

AU - Arnold, Norbert

AU - Niederacher, Dieter

AU - Sutter, Christian

AU - Gadzicki, Dorothea

AU - Fiebig, Britta

AU - Caldes, Trinidad

AU - Laframboise, Rachel

AU - Nevanlinna, Heli

AU - Chen, Xiaoqing

AU - Beesley, Jonathan

AU - Spurdle, Amanda B.

AU - Neuhausen, Susan L.

AU - Ding, Yuan C.

AU - Couch, Fergus J.

AU - Wang, Xianshu

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Bernard, Loris

AU - Radice, Paolo

AU - Easton, Douglas F.

AU - Chenevix-Trench, Georgia

AU - Antoniou, Antonis C.

AU - Stoppa-Lyonnet, Dominique

AU - Mazoyer, Sylvie

AU - Sinilnikova, Olga M.

AU - Olsson, Håkan

PY - 2011

Y1 - 2011

N2 - Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA1 gene would modify the risk of breast cancer in carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of breast cancer (hazard ratio 0.86, 95% confidence interval 0.77-0.95, P = 0.003). Promoter in vitro assays of the major BRCA1 haplotypes showed that common polymorphisms in the regulatory region alter its activity and that this effect may be attributed to the differential binding affinity of nuclear proteins. In conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1 transcription.

AB - Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA1 gene would modify the risk of breast cancer in carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of breast cancer (hazard ratio 0.86, 95% confidence interval 0.77-0.95, P = 0.003). Promoter in vitro assays of the major BRCA1 haplotypes showed that common polymorphisms in the regulatory region alter its activity and that this effect may be attributed to the differential binding affinity of nuclear proteins. In conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1 transcription.

U2 - 10.1093/hmg/ddr388

DO - 10.1093/hmg/ddr388

M3 - Article

VL - 20

SP - 4732

EP - 4747

JO - Human Molecular Genetics

T2 - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 23

ER -