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

David G. Cox, Jacques Simard, Daniel Sinnett, Yosr Hamdi, Penny Soucy, Manon Ouimet, Laure Barjhoux, Carole Verny-Pierre, Lesley McGuffog, Sue Healey, Csilla Szabo, Mark H. Greene, Phuong L. Mai, Irene L. Andrulis, Gord Glendon, Teresa Selander, Nayana Weerasooriya, Mads Thomassen, Anne Marie Gerdes, Maria A. CaligoEitan Friedman, Yael Laitman, Bella Kaufman, Shani S. Paluch, Åke Borg, Per Karlsson, Marie Stenmark Askmalm, Gisela Barbany Bustinza, Katherine L. Nathanson, Susan M. Domchek, Timothy R. Rebbeck, Javier Benítez, Ute Hamann, Matti A. Rookus, Ans M W van den Ouweland, Margreet G E M Ausems, Cora M. Aalfs, Christi J. van Asperen, Peter Devilee, Hans J J P Gille, Susan Peock, Debra Frost, D. Gareth Evans, Ros Eeles, Louise Izatt, LoeterDevilee Adlard, Joan Paterson, Jacqueline Eason, Andrew K. Godwin, Marie Alice Remon, Virginie Moncoutier, Marion Gauthier-Villars, Christine Lasset, Sophie Giraud, Agnès Hardouin, Pascaline Berthet, Hagay Sobol, François Eisinger, Brigitte Bressac de Paillerets, Olivier Caron, Capucine Delnatte, David Goldgar, Alex Miron, Hilmi Ozcelik, Saundra Buys, Melissa C. Southey, Mary Beth Terry, Christian F. Singer, Anne Catharina Dressler, Muy Kheng Tea, Thomas V O Hansen, Oskar Johannsson, Marion Piedmonte, Gustavo C. Rodriguez, Jack B. Basil, Stephanie Blank, Amanda E. Toland, Marco Montagna, Claudine Isaacs, Ignacio Blanco, Simon A. Gayther, Kirsten B. Moysich, Rita K. Schmutzler, Barbara Wappenschmidt, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Dieter Niederacher, Christian Sutter, Dorothea Gadzicki, Britta Fiebig, Trinidad Caldes, Rachel Laframboise, Heli Nevanlinna, Xiaoqing Chen, Jonathan Beesley, Amanda B. Spurdle, Susan L. Neuhausen, Yuan C. Ding, Fergus J Couch, Xianshu Wang, Paolo Peterlongo, Siranoush Manoukian, Loris Bernard, Paolo Radice, Douglas F. Easton, Georgia Chenevix-Trench, Antonis C. Antoniou, Dominique Stoppa-Lyonnet, Sylvie Mazoyer, Olga M. Sinilnikova, Per Karlsson, Margareta Nordling, Annika Bergman, Zakaria Einbeigi, Marie Stenmark-Askmalm, Sigrun Liedgren, Åke Borg, Niklas Loman, Håkan Olsson, Ulf Kristoffersson, Maria Soller, Helena Jernström, Katja Harbst, Karin Henriksson, Annika Lindblom, Brita Arver, Anna von Wachenfeldt, Annelie Liljegren, Gisela Barbany-Bustinza, Johanna Rantala, Beatrice Melin, Henrik Grönberg, Eva Lena Stattin, Monica Emanuelsson, Hans Ehrencrona, Richard Rosenquist Brandell, Niklas Dahl, F. B L Hogervorst, S. Verhoef, M. Verheus, L. J. van't Veer, F. E. van Leeuwen, M. A. Rookus, M. Collée, A. M W van den Ouweland, A. Jager, M. J. Hooning, M. M A Tilanus-Linthorst, C. Seynaeve, C. J. van Asperen, J. T. Wijnen, M. P. Vreeswijk, R. A. Tollenaar, P. Devilee, M. J. Ligtenberg, N. Hoogerbrugge, M. G. Ausems, R. B. van der Luijt, C. M. Aalfs, T. A. van Os, J. J P Gille, Q. Waisfisz, H. E J Meijers-Heijboer, E. B. Gomez-Garcia, C. E. van Roozendaal, Marinus J. Blok, B. Caanen, J. C. Oosterwijk, A. H. van der Hout, M. J. Mourits, H. F. Vasen, Susan Peock, Margaret Cook, Debra Frost, Radka Platte, Zosia Miedzybrodzka, Helen Gregory, Patrick Morrison, Lisa Jeffers, Trevor Cole, Kai Ren Ong, Jonathan Hoffman, Alan Donaldson, Margaret James, Joan Paterson, Sarah Downing, Amy Taylor, Alexandra Murray, Mark T. Rogers, Emma McCann, M. John Kennedy, David Barton, Mary Porteous, Sarah Drummond, Carole Brewer, Emma Kivuva, Anne Searle, Selina Goodman, Kathryn Hill, Rosemarie Davidson, Victoria Murday, Nicola Bradshaw, Lesley Snadden, Mark Longmuir, Catherine Watt, Sarah Gibson, Eshika Haque, Ed Tobias, Alexis Duncan, Louise Izatt, Chris Jacobs, Caroline Langman, Anna Whaite, Huw Dorkins, Julian Barwell, Julian Adlard, Carol Chu, Julie Miller, Ian Ellis, Catherine Houghton, D. Gareth Evans, Fiona Lalloo, Jane Taylor, Lucy Side, Alison Male, Cheryl Berlin, Jacqueline Eason, Rebecca Collier, Fiona Douglas, Oonagh Claber, Irene Jobson, Lisa Walker, Diane McLeod, Dorothy Halliday, Sarah Durell, Barbara Stayner, Ros Eeles, Susan Shanley, Nazneen Rahman, Richard Houlston, Elizabeth Bancroft, Lucia D'Mello, Elizabeth Page, Audrey Ardern-Jones, Kelly Kohut, Jennifer Wiggins, Elena Castro, Anita Mitra, Lisa Robertson, Jackie Cook, Oliver Quarrell, Cathryn Bardsley, Shirley Hodgson, Sheila Goff, Glen Brice, Lizzie Winchester, Charlotte Eddy, Vishakha Tripathi, Virginia Attard, Diana Eccles, Anneke Lucassen, Gillian Crawford, Donna McBride, Sarah Smalley, Olga Sinilnikova, Laure Barjhoux, Carole Verny-Pierre, Sophie Giraud, Mélanie Léone, Sylvie Mazoyer, Dominique Stoppa-Lyonnet, Marion Gauthier-Villars, Bruno Buecher, Claude Houdayer, Virginie Moncoutier, Muriel Belotti, Carole Tirapo, Antoine de Pauw, Brigitte Bressac-de-Paillerets, Audrey Remenieras, Véronique Byrde, Olivier Caron, Gilbert Lenoir, Yves Jean Bignon, Nancy Uhrhammer, Christine Lasset, Valérie Bonadona, Agnès Hardouin, Pascaline Berthet, Hagay Sobol, Violaine Bourdon, Tetsuro Noguchi, François Eisinger, Florence Coulet, Chrystelle Colas, Florent Soubrier, Isabelle Coupier, Pascal Pujol, Jean Philippe Peyrat, Joëlle Fournier, Françoise Révillion, Philippe Vennin, Claude Adenis, Etienne Rouleau, Rosette Lidereau, Liliane Demange, Catherine Nogues, Danièle Muller, Jean Pierre Fricker, Michel Longy, Nicolas Sevenet, Christine Toulas, Rosine Guimbaud, Laurence Gladieff, Viviane Feillel, Dominique Leroux, Hélène Dreyfus, Christine Rebischung, Fanny Coron, Laurence Faivre, Fabienne Prieur, Marine Lebrun, Sandra Fert Ferrer, Marc Frénay, Laurence Vénat-Bouvet

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 5 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.

Original languageEnglish (US)
Article numberddr388
Pages (from-to)4732-4747
Number of pages16
JournalHuman Molecular Genetics
Volume20
Issue number23
DOIs
StatePublished - Dec 2011

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Alleles
Breast Neoplasms
Mutation
BRCA1 Gene
Haplotypes
BRCA1 Protein
Nucleic Acid Regulatory Sequences
Nuclear Proteins
DNA Repair
Single Nucleotide Polymorphism
Carcinogenesis
Research Personnel
Confidence Intervals

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Cox, D. G., Simard, J., Sinnett, D., Hamdi, Y., Soucy, P., Ouimet, M., ... Vénat-Bouvet, L. (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. [ddr388]. https://doi.org/10.1093/hmg/ddr388

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.; Glendon, Gord; Selander, Teresa; Weerasooriya, Nayana; 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.; Benítez, 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, LoeterDevilee; Paterson, Joan; Eason, Jacqueline; Godwin, Andrew K.; Remon, Marie Alice; Moncoutier, Virginie; Gauthier-Villars, Marion; Lasset, Christine; Giraud, Sophie; Hardouin, Agnès; Berthet, Pascaline; Sobol, Hagay; Eisinger, François; 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.; Karlsson, Per; Nordling, Margareta; Bergman, Annika; Einbeigi, Zakaria; Stenmark-Askmalm, Marie; Liedgren, Sigrun; Borg, Åke; Loman, Niklas; Olsson, Håkan; Kristoffersson, Ulf; Soller, Maria; Jernström, Helena; Harbst, Katja; Henriksson, Karin; Lindblom, Annika; Arver, Brita; von Wachenfeldt, Anna; Liljegren, Annelie; Barbany-Bustinza, Gisela; Rantala, Johanna; Melin, Beatrice; Grönberg, Henrik; Stattin, Eva Lena; Emanuelsson, Monica; Ehrencrona, Hans; Brandell, Richard Rosenquist; Dahl, Niklas; Hogervorst, F. B L; Verhoef, S.; Verheus, M.; van't Veer, L. J.; van Leeuwen, F. E.; Rookus, M. A.; Collée, M.; van den Ouweland, A. M W; Jager, A.; Hooning, M. J.; Tilanus-Linthorst, M. M A; Seynaeve, C.; van Asperen, C. J.; Wijnen, J. T.; Vreeswijk, M. P.; Tollenaar, R. A.; Devilee, P.; Ligtenberg, M. J.; Hoogerbrugge, N.; Ausems, M. G.; van der Luijt, R. B.; Aalfs, C. M.; van Os, T. A.; Gille, J. J P; Waisfisz, Q.; Meijers-Heijboer, H. E J; Gomez-Garcia, E. B.; van Roozendaal, C. E.; Blok, Marinus J.; Caanen, B.; Oosterwijk, J. C.; van der Hout, A. H.; Mourits, M. J.; Vasen, H. F.; Peock, Susan; Cook, Margaret; Frost, Debra; Platte, Radka; Miedzybrodzka, Zosia; Gregory, Helen; Morrison, Patrick; Jeffers, Lisa; Cole, Trevor; Ong, Kai Ren; Hoffman, Jonathan; Donaldson, Alan; James, Margaret; Paterson, Joan; Downing, Sarah; Taylor, Amy; Murray, Alexandra; Rogers, Mark T.; McCann, Emma; Kennedy, M. John; Barton, David; Porteous, Mary; Drummond, Sarah; Brewer, Carole; Kivuva, Emma; Searle, Anne; Goodman, Selina; Hill, Kathryn; Davidson, Rosemarie; Murday, Victoria; Bradshaw, Nicola; Snadden, Lesley; Longmuir, Mark; Watt, Catherine; Gibson, Sarah; Haque, Eshika; Tobias, Ed; Duncan, Alexis; Izatt, Louise; Jacobs, Chris; Langman, Caroline; Whaite, Anna; Dorkins, Huw; Barwell, Julian; Adlard, Julian; Chu, Carol; Miller, Julie; Ellis, Ian; Houghton, Catherine; Evans, D. Gareth; Lalloo, Fiona; Taylor, Jane; Side, Lucy; Male, Alison; Berlin, Cheryl; Eason, Jacqueline; Collier, Rebecca; Douglas, Fiona; Claber, Oonagh; Jobson, Irene; Walker, Lisa; McLeod, Diane; Halliday, Dorothy; Durell, Sarah; Stayner, Barbara; Eeles, Ros; Shanley, Susan; Rahman, Nazneen; Houlston, Richard; Bancroft, Elizabeth; D'Mello, Lucia; Page, Elizabeth; Ardern-Jones, Audrey; Kohut, Kelly; Wiggins, Jennifer; Castro, Elena; Mitra, Anita; Robertson, Lisa; Cook, Jackie; Quarrell, Oliver; Bardsley, Cathryn; Hodgson, Shirley; Goff, Sheila; Brice, Glen; Winchester, Lizzie; Eddy, Charlotte; Tripathi, Vishakha; Attard, Virginia; Eccles, Diana; Lucassen, Anneke; Crawford, Gillian; McBride, Donna; Smalley, Sarah; Sinilnikova, Olga; Barjhoux, Laure; Verny-Pierre, Carole; Giraud, Sophie; Léone, Mélanie; Mazoyer, Sylvie; Stoppa-Lyonnet, Dominique; Gauthier-Villars, Marion; Buecher, Bruno; Houdayer, Claude; Moncoutier, Virginie; Belotti, Muriel; Tirapo, Carole; de Pauw, Antoine; Bressac-de-Paillerets, Brigitte; Remenieras, Audrey; Byrde, Véronique; Caron, Olivier; Lenoir, Gilbert; Bignon, Yves Jean; Uhrhammer, Nancy; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Sobol, Hagay; Bourdon, Violaine; Noguchi, Tetsuro; Eisinger, François; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Coupier, Isabelle; Pujol, Pascal; Peyrat, Jean Philippe; Fournier, Joëlle; Révillion, Françoise; Vennin, Philippe; Adenis, Claude; Rouleau, Etienne; Lidereau, Rosette; Demange, Liliane; Nogues, Catherine; Muller, Danièle; Fricker, Jean Pierre; Longy, Michel; Sevenet, Nicolas; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Leroux, Dominique; Dreyfus, Hélène; Rebischung, Christine; Coron, Fanny; Faivre, Laurence; Prieur, Fabienne; Lebrun, Marine; Ferrer, Sandra Fert; Frénay, Marc; Vénat-Bouvet, Laurence.

In: Human Molecular Genetics, Vol. 20, No. 23, ddr388, 12.2011, p. 4732-4747.

Research output: Contribution to journalArticle

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, Glendon, G, Selander, T, Weerasooriya, N, Thomassen, M, Gerdes, AM, Caligo, MA, Friedman, E, Laitman, Y, Kaufman, B, Paluch, SS, Borg, Å, Karlsson, P, Askmalm, MS, Bustinza, GB, Nathanson, KL, Domchek, SM, Rebbeck, TR, Benítez, 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, L, Paterson, J, Eason, J, Godwin, AK, Remon, MA, 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, AC, Tea, MK, 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, Karlsson, P, Nordling, M, Bergman, A, Einbeigi, Z, Stenmark-Askmalm, M, Liedgren, S, Borg, Å, Loman, N, Olsson, H, Kristoffersson, U, Soller, M, Jernström, H, Harbst, K, Henriksson, K, Lindblom, A, Arver, B, von Wachenfeldt, A, Liljegren, A, Barbany-Bustinza, G, Rantala, J, Melin, B, Grönberg, H, Stattin, EL, Emanuelsson, M, Ehrencrona, H, Brandell, RR, Dahl, N, Hogervorst, FBL, Verhoef, S, Verheus, M, van't Veer, LJ, van Leeuwen, FE, Rookus, MA, Collée, M, van den Ouweland, AMW, Jager, A, Hooning, MJ, Tilanus-Linthorst, MMA, Seynaeve, C, van Asperen, CJ, Wijnen, JT, Vreeswijk, MP, Tollenaar, RA, Devilee, P, Ligtenberg, MJ, Hoogerbrugge, N, Ausems, MG, van der Luijt, RB, Aalfs, CM, van Os, TA, Gille, JJP, Waisfisz, Q, Meijers-Heijboer, HEJ, Gomez-Garcia, EB, van Roozendaal, CE, Blok, MJ, Caanen, B, Oosterwijk, JC, van der Hout, AH, Mourits, MJ, Vasen, HF, Peock, S, Cook, M, Frost, D, Platte, R, Miedzybrodzka, Z, Gregory, H, Morrison, P, Jeffers, L, Cole, T, Ong, KR, Hoffman, J, Donaldson, A, James, M, Paterson, J, Downing, S, Taylor, A, Murray, A, Rogers, MT, McCann, E, Kennedy, MJ, Barton, D, Porteous, M, Drummond, S, Brewer, C, Kivuva, E, Searle, A, Goodman, S, Hill, K, Davidson, R, Murday, V, Bradshaw, N, Snadden, L, Longmuir, M, Watt, C, Gibson, S, Haque, E, Tobias, E, Duncan, A, Izatt, L, Jacobs, C, Langman, C, Whaite, A, Dorkins, H, Barwell, J, Adlard, J, Chu, C, Miller, J, Ellis, I, Houghton, C, Evans, DG, Lalloo, F, Taylor, J, Side, L, Male, A, Berlin, C, Eason, J, Collier, R, Douglas, F, Claber, O, Jobson, I, Walker, L, McLeod, D, Halliday, D, Durell, S, Stayner, B, Eeles, R, Shanley, S, Rahman, N, Houlston, R, Bancroft, E, D'Mello, L, Page, E, Ardern-Jones, A, Kohut, K, Wiggins, J, Castro, E, Mitra, A, Robertson, L, Cook, J, Quarrell, O, Bardsley, C, Hodgson, S, Goff, S, Brice, G, Winchester, L, Eddy, C, Tripathi, V, Attard, V, Eccles, D, Lucassen, A, Crawford, G, McBride, D, Smalley, S, Sinilnikova, O, Barjhoux, L, Verny-Pierre, C, Giraud, S, Léone, M, Mazoyer, S, Stoppa-Lyonnet, D, Gauthier-Villars, M, Buecher, B, Houdayer, C, Moncoutier, V, Belotti, M, Tirapo, C, de Pauw, A, Bressac-de-Paillerets, B, Remenieras, A, Byrde, V, Caron, O, Lenoir, G, Bignon, YJ, Uhrhammer, N, Lasset, C, Bonadona, V, Hardouin, A, Berthet, P, Sobol, H, Bourdon, V, Noguchi, T, Eisinger, F, Coulet, F, Colas, C, Soubrier, F, Coupier, I, Pujol, P, Peyrat, JP, Fournier, J, Révillion, F, Vennin, P, Adenis, C, Rouleau, E, Lidereau, R, Demange, L, Nogues, C, Muller, D, Fricker, JP, Longy, M, Sevenet, N, Toulas, C, Guimbaud, R, Gladieff, L, Feillel, V, Leroux, D, Dreyfus, H, Rebischung, C, Coron, F, Faivre, L, Prieur, F, Lebrun, M, Ferrer, SF, Frénay, M & Vénat-Bouvet, L 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, ddr388, pp. 4732-4747. https://doi.org/10.1093/hmg/ddr388
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. ; Glendon, Gord ; Selander, Teresa ; Weerasooriya, Nayana ; 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. ; Benítez, 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, LoeterDevilee ; Paterson, Joan ; Eason, Jacqueline ; Godwin, Andrew K. ; Remon, Marie Alice ; Moncoutier, Virginie ; Gauthier-Villars, Marion ; Lasset, Christine ; Giraud, Sophie ; Hardouin, Agnès ; Berthet, Pascaline ; Sobol, Hagay ; Eisinger, François ; 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. ; Karlsson, Per ; Nordling, Margareta ; Bergman, Annika ; Einbeigi, Zakaria ; Stenmark-Askmalm, Marie ; Liedgren, Sigrun ; Borg, Åke ; Loman, Niklas ; Olsson, Håkan ; Kristoffersson, Ulf ; Soller, Maria ; Jernström, Helena ; Harbst, Katja ; Henriksson, Karin ; Lindblom, Annika ; Arver, Brita ; von Wachenfeldt, Anna ; Liljegren, Annelie ; Barbany-Bustinza, Gisela ; Rantala, Johanna ; Melin, Beatrice ; Grönberg, Henrik ; Stattin, Eva Lena ; Emanuelsson, Monica ; Ehrencrona, Hans ; Brandell, Richard Rosenquist ; Dahl, Niklas ; Hogervorst, F. B L ; Verhoef, S. ; Verheus, M. ; van't Veer, L. J. ; van Leeuwen, F. E. ; Rookus, M. A. ; Collée, M. ; van den Ouweland, A. M W ; Jager, A. ; Hooning, M. J. ; Tilanus-Linthorst, M. M A ; Seynaeve, C. ; van Asperen, C. J. ; Wijnen, J. T. ; Vreeswijk, M. P. ; Tollenaar, R. A. ; Devilee, P. ; Ligtenberg, M. J. ; Hoogerbrugge, N. ; Ausems, M. G. ; van der Luijt, R. B. ; Aalfs, C. M. ; van Os, T. A. ; Gille, J. J P ; Waisfisz, Q. ; Meijers-Heijboer, H. E J ; Gomez-Garcia, E. B. ; van Roozendaal, C. E. ; Blok, Marinus J. ; Caanen, B. ; Oosterwijk, J. C. ; van der Hout, A. H. ; Mourits, M. J. ; Vasen, H. F. ; Peock, Susan ; Cook, Margaret ; Frost, Debra ; Platte, Radka ; Miedzybrodzka, Zosia ; Gregory, Helen ; Morrison, Patrick ; Jeffers, Lisa ; Cole, Trevor ; Ong, Kai Ren ; Hoffman, Jonathan ; Donaldson, Alan ; James, Margaret ; Paterson, Joan ; Downing, Sarah ; Taylor, Amy ; Murray, Alexandra ; Rogers, Mark T. ; McCann, Emma ; Kennedy, M. John ; Barton, David ; Porteous, Mary ; Drummond, Sarah ; Brewer, Carole ; Kivuva, Emma ; Searle, Anne ; Goodman, Selina ; Hill, Kathryn ; Davidson, Rosemarie ; Murday, Victoria ; Bradshaw, Nicola ; Snadden, Lesley ; Longmuir, Mark ; Watt, Catherine ; Gibson, Sarah ; Haque, Eshika ; Tobias, Ed ; Duncan, Alexis ; Izatt, Louise ; Jacobs, Chris ; Langman, Caroline ; Whaite, Anna ; Dorkins, Huw ; Barwell, Julian ; Adlard, Julian ; Chu, Carol ; Miller, Julie ; Ellis, Ian ; Houghton, Catherine ; Evans, D. Gareth ; Lalloo, Fiona ; Taylor, Jane ; Side, Lucy ; Male, Alison ; Berlin, Cheryl ; Eason, Jacqueline ; Collier, Rebecca ; Douglas, Fiona ; Claber, Oonagh ; Jobson, Irene ; Walker, Lisa ; McLeod, Diane ; Halliday, Dorothy ; Durell, Sarah ; Stayner, Barbara ; Eeles, Ros ; Shanley, Susan ; Rahman, Nazneen ; Houlston, Richard ; Bancroft, Elizabeth ; D'Mello, Lucia ; Page, Elizabeth ; Ardern-Jones, Audrey ; Kohut, Kelly ; Wiggins, Jennifer ; Castro, Elena ; Mitra, Anita ; Robertson, Lisa ; Cook, Jackie ; Quarrell, Oliver ; Bardsley, Cathryn ; Hodgson, Shirley ; Goff, Sheila ; Brice, Glen ; Winchester, Lizzie ; Eddy, Charlotte ; Tripathi, Vishakha ; Attard, Virginia ; Eccles, Diana ; Lucassen, Anneke ; Crawford, Gillian ; McBride, Donna ; Smalley, Sarah ; Sinilnikova, Olga ; Barjhoux, Laure ; Verny-Pierre, Carole ; Giraud, Sophie ; Léone, Mélanie ; Mazoyer, Sylvie ; Stoppa-Lyonnet, Dominique ; Gauthier-Villars, Marion ; Buecher, Bruno ; Houdayer, Claude ; Moncoutier, Virginie ; Belotti, Muriel ; Tirapo, Carole ; de Pauw, Antoine ; Bressac-de-Paillerets, Brigitte ; Remenieras, Audrey ; Byrde, Véronique ; Caron, Olivier ; Lenoir, Gilbert ; Bignon, Yves Jean ; Uhrhammer, Nancy ; Lasset, Christine ; Bonadona, Valérie ; Hardouin, Agnès ; Berthet, Pascaline ; Sobol, Hagay ; Bourdon, Violaine ; Noguchi, Tetsuro ; Eisinger, François ; Coulet, Florence ; Colas, Chrystelle ; Soubrier, Florent ; Coupier, Isabelle ; Pujol, Pascal ; Peyrat, Jean Philippe ; Fournier, Joëlle ; Révillion, Françoise ; Vennin, Philippe ; Adenis, Claude ; Rouleau, Etienne ; Lidereau, Rosette ; Demange, Liliane ; Nogues, Catherine ; Muller, Danièle ; Fricker, Jean Pierre ; Longy, Michel ; Sevenet, Nicolas ; Toulas, Christine ; Guimbaud, Rosine ; Gladieff, Laurence ; Feillel, Viviane ; Leroux, Dominique ; Dreyfus, Hélène ; Rebischung, Christine ; Coron, Fanny ; Faivre, Laurence ; Prieur, Fabienne ; Lebrun, Marine ; Ferrer, Sandra Fert ; Frénay, Marc ; Vénat-Bouvet, Laurence. / 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.
@article{a515c8442e4b400abbb9abdf642e1c62,
title = "Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers",
abstract = "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 5 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.",
author = "Cox, {David G.} and Jacques Simard and Daniel Sinnett and Yosr Hamdi and Penny Soucy and Manon Ouimet and Laure Barjhoux and Carole Verny-Pierre and Lesley McGuffog and Sue Healey and Csilla Szabo and Greene, {Mark H.} and Mai, {Phuong L.} and Andrulis, {Irene L.} and Gord Glendon and Teresa Selander and Nayana Weerasooriya and Mads Thomassen and Gerdes, {Anne Marie} and Caligo, {Maria A.} and Eitan Friedman and Yael Laitman and Bella Kaufman and Paluch, {Shani S.} and {\AA}ke Borg and Per Karlsson and Askmalm, {Marie Stenmark} and Bustinza, {Gisela Barbany} and Nathanson, {Katherine L.} and Domchek, {Susan M.} and Rebbeck, {Timothy R.} and Javier Ben{\'i}tez and Ute Hamann and Rookus, {Matti A.} and {van den Ouweland}, {Ans M W} and Ausems, {Margreet G E M} and Aalfs, {Cora M.} and {van Asperen}, {Christi J.} and Peter Devilee and Gille, {Hans J J P} and Susan Peock and Debra Frost and Evans, {D. Gareth} and Ros Eeles and Louise Izatt and LoeterDevilee Adlard and Joan Paterson and Jacqueline Eason and Godwin, {Andrew K.} and Remon, {Marie Alice} and Virginie Moncoutier and Marion Gauthier-Villars and Christine Lasset and Sophie Giraud and Agn{\`e}s Hardouin and Pascaline Berthet and Hagay Sobol and Fran{\cc}ois Eisinger and {de Paillerets}, {Brigitte Bressac} and Olivier Caron and Capucine Delnatte and David Goldgar and Alex Miron and Hilmi Ozcelik and Saundra Buys and Southey, {Melissa C.} and Terry, {Mary Beth} and Singer, {Christian F.} and Dressler, {Anne Catharina} and Tea, {Muy Kheng} and Hansen, {Thomas V O} and Oskar Johannsson and Marion Piedmonte and Rodriguez, {Gustavo C.} and Basil, {Jack B.} and Stephanie Blank and Toland, {Amanda E.} and Marco Montagna and Claudine Isaacs and Ignacio Blanco and Gayther, {Simon A.} and Moysich, {Kirsten B.} and Schmutzler, {Rita K.} and Barbara Wappenschmidt and Christoph Engel and Alfons Meindl and Nina Ditsch and Norbert Arnold and Dieter Niederacher and Christian Sutter and Dorothea Gadzicki and Britta Fiebig and Trinidad Caldes and Rachel Laframboise and Heli Nevanlinna and Xiaoqing Chen and Jonathan Beesley and Spurdle, {Amanda B.} and Neuhausen, {Susan L.} and Ding, {Yuan C.} and Couch, {Fergus J} and Xianshu Wang and Paolo Peterlongo and Siranoush Manoukian and Loris Bernard and Paolo Radice and Easton, {Douglas F.} and Georgia Chenevix-Trench and Antoniou, {Antonis C.} and Dominique Stoppa-Lyonnet and Sylvie Mazoyer and Sinilnikova, {Olga M.} and Per Karlsson and Margareta Nordling and Annika Bergman and Zakaria Einbeigi and Marie Stenmark-Askmalm and Sigrun Liedgren and {\AA}ke Borg and Niklas Loman and H{\aa}kan Olsson and Ulf Kristoffersson and Maria Soller and Helena Jernstr{\"o}m and Katja Harbst and Karin Henriksson and Annika Lindblom and Brita Arver and {von Wachenfeldt}, Anna and Annelie Liljegren and Gisela Barbany-Bustinza and Johanna Rantala and Beatrice Melin and Henrik Gr{\"o}nberg and Stattin, {Eva Lena} and Monica Emanuelsson and Hans Ehrencrona and Brandell, {Richard Rosenquist} and Niklas Dahl and Hogervorst, {F. B L} and S. Verhoef and M. Verheus and {van't Veer}, {L. J.} and {van Leeuwen}, {F. E.} and Rookus, {M. A.} and M. Coll{\'e}e and {van den Ouweland}, {A. M W} and A. Jager and Hooning, {M. J.} and Tilanus-Linthorst, {M. M A} and C. Seynaeve and {van Asperen}, {C. J.} and Wijnen, {J. T.} and Vreeswijk, {M. P.} and Tollenaar, {R. A.} and P. Devilee and Ligtenberg, {M. J.} and N. Hoogerbrugge and Ausems, {M. G.} and {van der Luijt}, {R. B.} and Aalfs, {C. M.} and {van Os}, {T. A.} and Gille, {J. J P} and Q. Waisfisz and Meijers-Heijboer, {H. E J} and Gomez-Garcia, {E. B.} and {van Roozendaal}, {C. E.} and Blok, {Marinus J.} and B. Caanen and Oosterwijk, {J. C.} and {van der Hout}, {A. H.} and Mourits, {M. J.} and Vasen, {H. F.} and Susan Peock and Margaret Cook and Debra Frost and Radka Platte and Zosia Miedzybrodzka and Helen Gregory and Patrick Morrison and Lisa Jeffers and Trevor Cole and Ong, {Kai Ren} and Jonathan Hoffman and Alan Donaldson and Margaret James and Joan Paterson and Sarah Downing and Amy Taylor and Alexandra Murray and Rogers, {Mark T.} and Emma McCann and Kennedy, {M. John} and David Barton and Mary Porteous and Sarah Drummond and Carole Brewer and Emma Kivuva and Anne Searle and Selina Goodman and Kathryn Hill and Rosemarie Davidson and Victoria Murday and Nicola Bradshaw and Lesley Snadden and Mark Longmuir and Catherine Watt and Sarah Gibson and Eshika Haque and Ed Tobias and Alexis Duncan and Louise Izatt and Chris Jacobs and Caroline Langman and Anna Whaite and Huw Dorkins and Julian Barwell and Julian Adlard and Carol Chu and Julie Miller and Ian Ellis and Catherine Houghton and Evans, {D. Gareth} and Fiona Lalloo and Jane Taylor and Lucy Side and Alison Male and Cheryl Berlin and Jacqueline Eason and Rebecca Collier and Fiona Douglas and Oonagh Claber and Irene Jobson and Lisa Walker and Diane McLeod and Dorothy Halliday and Sarah Durell and Barbara Stayner and Ros Eeles and Susan Shanley and Nazneen Rahman and Richard Houlston and Elizabeth Bancroft and Lucia D'Mello and Elizabeth Page and Audrey Ardern-Jones and Kelly Kohut and Jennifer Wiggins and Elena Castro and Anita Mitra and Lisa Robertson and Jackie Cook and Oliver Quarrell and Cathryn Bardsley and Shirley Hodgson and Sheila Goff and Glen Brice and Lizzie Winchester and Charlotte Eddy and Vishakha Tripathi and Virginia Attard and Diana Eccles and Anneke Lucassen and Gillian Crawford and Donna McBride and Sarah Smalley and Olga Sinilnikova and Laure Barjhoux and Carole Verny-Pierre and Sophie Giraud and M{\'e}lanie L{\'e}one and Sylvie Mazoyer and Dominique Stoppa-Lyonnet and Marion Gauthier-Villars and Bruno Buecher and Claude Houdayer and Virginie Moncoutier and Muriel Belotti and Carole Tirapo and {de Pauw}, Antoine and Brigitte Bressac-de-Paillerets and Audrey Remenieras and V{\'e}ronique Byrde and Olivier Caron and Gilbert Lenoir and Bignon, {Yves Jean} and Nancy Uhrhammer and Christine Lasset and Val{\'e}rie Bonadona and Agn{\`e}s Hardouin and Pascaline Berthet and Hagay Sobol and Violaine Bourdon and Tetsuro Noguchi and Fran{\cc}ois Eisinger and Florence Coulet and Chrystelle Colas and Florent Soubrier and Isabelle Coupier and Pascal Pujol and Peyrat, {Jean Philippe} and Jo{\"e}lle Fournier and Fran{\cc}oise R{\'e}villion and Philippe Vennin and Claude Adenis and Etienne Rouleau and Rosette Lidereau and Liliane Demange and Catherine Nogues and Dani{\`e}le Muller and Fricker, {Jean Pierre} and Michel Longy and Nicolas Sevenet and Christine Toulas and Rosine Guimbaud and Laurence Gladieff and Viviane Feillel and Dominique Leroux and H{\'e}l{\`e}ne Dreyfus and Christine Rebischung and Fanny Coron and Laurence Faivre and Fabienne Prieur and Marine Lebrun and Ferrer, {Sandra Fert} and Marc Fr{\'e}nay and Laurence V{\'e}nat-Bouvet",
year = "2011",
month = "12",
doi = "10.1093/hmg/ddr388",
language = "English (US)",
volume = "20",
pages = "4732--4747",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "23",

}

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 - Glendon, Gord

AU - Selander, Teresa

AU - Weerasooriya, Nayana

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 - Benítez, 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, LoeterDevilee

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, Agnès

AU - Berthet, Pascaline

AU - Sobol, Hagay

AU - Eisinger, François

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 - Karlsson, Per

AU - Nordling, Margareta

AU - Bergman, Annika

AU - Einbeigi, Zakaria

AU - Stenmark-Askmalm, Marie

AU - Liedgren, Sigrun

AU - Borg, Åke

AU - Loman, Niklas

AU - Olsson, Håkan

AU - Kristoffersson, Ulf

AU - Soller, Maria

AU - Jernström, Helena

AU - Harbst, Katja

AU - Henriksson, Karin

AU - Lindblom, Annika

AU - Arver, Brita

AU - von Wachenfeldt, Anna

AU - Liljegren, Annelie

AU - Barbany-Bustinza, Gisela

AU - Rantala, Johanna

AU - Melin, Beatrice

AU - Grönberg, Henrik

AU - Stattin, Eva Lena

AU - Emanuelsson, Monica

AU - Ehrencrona, Hans

AU - Brandell, Richard Rosenquist

AU - Dahl, Niklas

AU - Hogervorst, F. B L

AU - Verhoef, S.

AU - Verheus, M.

AU - van't Veer, L. J.

AU - van Leeuwen, F. E.

AU - Rookus, M. A.

AU - Collée, M.

AU - van den Ouweland, A. M W

AU - Jager, A.

AU - Hooning, M. J.

AU - Tilanus-Linthorst, M. M A

AU - Seynaeve, C.

AU - van Asperen, C. J.

AU - Wijnen, J. T.

AU - Vreeswijk, M. P.

AU - Tollenaar, R. A.

AU - Devilee, P.

AU - Ligtenberg, M. J.

AU - Hoogerbrugge, N.

AU - Ausems, M. G.

AU - van der Luijt, R. B.

AU - Aalfs, C. M.

AU - van Os, T. A.

AU - Gille, J. J P

AU - Waisfisz, Q.

AU - Meijers-Heijboer, H. E J

AU - Gomez-Garcia, E. B.

AU - van Roozendaal, C. E.

AU - Blok, Marinus J.

AU - Caanen, B.

AU - Oosterwijk, J. C.

AU - van der Hout, A. H.

AU - Mourits, M. J.

AU - Vasen, H. F.

AU - Peock, Susan

AU - Cook, Margaret

AU - Frost, Debra

AU - Platte, Radka

AU - Miedzybrodzka, Zosia

AU - Gregory, Helen

AU - Morrison, Patrick

AU - Jeffers, Lisa

AU - Cole, Trevor

AU - Ong, Kai Ren

AU - Hoffman, Jonathan

AU - Donaldson, Alan

AU - James, Margaret

AU - Paterson, Joan

AU - Downing, Sarah

AU - Taylor, Amy

AU - Murray, Alexandra

AU - Rogers, Mark T.

AU - McCann, Emma

AU - Kennedy, M. John

AU - Barton, David

AU - Porteous, Mary

AU - Drummond, Sarah

AU - Brewer, Carole

AU - Kivuva, Emma

AU - Searle, Anne

AU - Goodman, Selina

AU - Hill, Kathryn

AU - Davidson, Rosemarie

AU - Murday, Victoria

AU - Bradshaw, Nicola

AU - Snadden, Lesley

AU - Longmuir, Mark

AU - Watt, Catherine

AU - Gibson, Sarah

AU - Haque, Eshika

AU - Tobias, Ed

AU - Duncan, Alexis

AU - Izatt, Louise

AU - Jacobs, Chris

AU - Langman, Caroline

AU - Whaite, Anna

AU - Dorkins, Huw

AU - Barwell, Julian

AU - Adlard, Julian

AU - Chu, Carol

AU - Miller, Julie

AU - Ellis, Ian

AU - Houghton, Catherine

AU - Evans, D. Gareth

AU - Lalloo, Fiona

AU - Taylor, Jane

AU - Side, Lucy

AU - Male, Alison

AU - Berlin, Cheryl

AU - Eason, Jacqueline

AU - Collier, Rebecca

AU - Douglas, Fiona

AU - Claber, Oonagh

AU - Jobson, Irene

AU - Walker, Lisa

AU - McLeod, Diane

AU - Halliday, Dorothy

AU - Durell, Sarah

AU - Stayner, Barbara

AU - Eeles, Ros

AU - Shanley, Susan

AU - Rahman, Nazneen

AU - Houlston, Richard

AU - Bancroft, Elizabeth

AU - D'Mello, Lucia

AU - Page, Elizabeth

AU - Ardern-Jones, Audrey

AU - Kohut, Kelly

AU - Wiggins, Jennifer

AU - Castro, Elena

AU - Mitra, Anita

AU - Robertson, Lisa

AU - Cook, Jackie

AU - Quarrell, Oliver

AU - Bardsley, Cathryn

AU - Hodgson, Shirley

AU - Goff, Sheila

AU - Brice, Glen

AU - Winchester, Lizzie

AU - Eddy, Charlotte

AU - Tripathi, Vishakha

AU - Attard, Virginia

AU - Eccles, Diana

AU - Lucassen, Anneke

AU - Crawford, Gillian

AU - McBride, Donna

AU - Smalley, Sarah

AU - Sinilnikova, Olga

AU - Barjhoux, Laure

AU - Verny-Pierre, Carole

AU - Giraud, Sophie

AU - Léone, Mélanie

AU - Mazoyer, Sylvie

AU - Stoppa-Lyonnet, Dominique

AU - Gauthier-Villars, Marion

AU - Buecher, Bruno

AU - Houdayer, Claude

AU - Moncoutier, Virginie

AU - Belotti, Muriel

AU - Tirapo, Carole

AU - de Pauw, Antoine

AU - Bressac-de-Paillerets, Brigitte

AU - Remenieras, Audrey

AU - Byrde, Véronique

AU - Caron, Olivier

AU - Lenoir, Gilbert

AU - Bignon, Yves Jean

AU - Uhrhammer, Nancy

AU - Lasset, Christine

AU - Bonadona, Valérie

AU - Hardouin, Agnès

AU - Berthet, Pascaline

AU - Sobol, Hagay

AU - Bourdon, Violaine

AU - Noguchi, Tetsuro

AU - Eisinger, François

AU - Coulet, Florence

AU - Colas, Chrystelle

AU - Soubrier, Florent

AU - Coupier, Isabelle

AU - Pujol, Pascal

AU - Peyrat, Jean Philippe

AU - Fournier, Joëlle

AU - Révillion, Françoise

AU - Vennin, Philippe

AU - Adenis, Claude

AU - Rouleau, Etienne

AU - Lidereau, Rosette

AU - Demange, Liliane

AU - Nogues, Catherine

AU - Muller, Danièle

AU - Fricker, Jean Pierre

AU - Longy, Michel

AU - Sevenet, Nicolas

AU - Toulas, Christine

AU - Guimbaud, Rosine

AU - Gladieff, Laurence

AU - Feillel, Viviane

AU - Leroux, Dominique

AU - Dreyfus, Hélène

AU - Rebischung, Christine

AU - Coron, Fanny

AU - Faivre, Laurence

AU - Prieur, Fabienne

AU - Lebrun, Marine

AU - Ferrer, Sandra Fert

AU - Frénay, Marc

AU - Vénat-Bouvet, Laurence

PY - 2011/12

Y1 - 2011/12

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 5 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 5 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.

UR - http://www.scopus.com/inward/record.url?scp=81255190718&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81255190718&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddr388

DO - 10.1093/hmg/ddr388

M3 - Article

C2 - 21890493

AN - SCOPUS:81255190718

VL - 20

SP - 4732

EP - 4747

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 23

M1 - ddr388

ER -