Abstract
Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r2 = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 × 10-9 for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10-8 for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
| Original language | English |
|---|---|
| Article number | ddr226 |
| Pages (from-to) | 3304-3321 |
| Number of pages | 18 |
| Journal | Human Molecular Genetics |
| Volume | 20 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - Aug 2011 |
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
- Molecular Biology
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers. / Antoniou, Antonis C.; Kartsonaki, Christiana; Sinilnikova, Olga M.; Soucy, Penny; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Cattaneo, Elisa; Barile, Monica; Pensotti, Valeria; Pasini, Barbara; Dolcetti, Riccardo; Giannini, Giuseppe; Putignano, Anna Laura; Varesco, Liliana; Radice, Paolo; Mai, Phuong L.; Greene, Mark H.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Thomassen, Mads; Gerdes, Anne Marie; Kruse, Torben A.; Jensen, Uffe Birk; Crüger, Dorthe G.; Caligo, Maria A.; Laitman, Yael; Milgrom, Roni; Kaufman, Bella; Paluch-Shimon, Shani; Friedman, Eitan; Loman, Niklas; Harbst, Katja; Lindblom, Annika; Arver, Brita; Ehrencrona, Hans; Melin, Beatrice; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy; Jakubowska, Ania; Lubinski, Jan; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Gorski, Bohdan; Osorio, Ana; Cajal, Teresa Ramón; Fostira, Florentia; Andrés, Raquel; Benitez, Javier; Hamann, Ute; Hogervorst, Frans B.; Rookus, Matti A.; Hooning, Maartje J.; Nelen, Marcel R.; van der Luijt, Rob B.; van Os, Theo A M; van Asperen, Christi J.; Devilee, Peter; Meijers-Heijboer, Hanne E J; Garcia, Encarna B Gómez; Peock, Susan; Cook, Margaret; Frost, D.; Platte, Radka; Leyland, Jean; Evans, D. Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Ong, Kai Ren; Cook, Jackie; Douglas, Fiona; Paterson, Joan; Kennedy, M. John; Miedzybrodzka, Zosia; Godwin, Andrew; Stoppa-Lyonnet, Dominique; Buecher, Bruno; Belotti, Muriel; Tirapo, Carole; Mazoyer, Sylvie; Barjhoux, Laure; Lasset, Christine; Leroux, Dominique; Faivre, Laurence; Bronner, Myriam; Prieur, Fabienne; Nogues, Catherine; Rouleau, Etienne; Pujol, Pascal; Coupier, Isabelle; Frénay, Marc; Hopper, John L.; Daly, Mary B.; Terry, Mary B.; John, Esther M.; Buys, Saundra S.; Yassin, Yosuf; Miron, Alexander; Goldgar, David; Singer, Christian F.; Tea, Muy Kheng; Pfeiler, Georg; Dressler, Anne Catharina; Hansen, Thomas v O; Jønson, Lars; Ejlertsen, Bent; Barkardottir, Rosa Bjork; Kirchhoff, Tomas; Offit, Kenneth; Piedmonte, Marion; Rodriguez, Gustavo; Small, Laurie; Boggess, John; Blank, Stephanie; Basil, Jack; Azodi, Masoud; Toland, Amanda Ewart; Montagna, Marco; Tognazzo, Silvia; Agata, Simona; Imyanitov, Evgeny; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Pharoah, Paul D P; Sucheston, Lara; Karlan, Beth Y.; Walsh, Christine S.; Olah, Edith; Bozsik, Aniko; Teo, Soo Hwang; Seldon, Joyce L.; Beattie, Mary S.; van Rensburg, Elizabeth J.; Sluiter, Michelle D.; Diez, Orland; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ruehl, Ina; Varon-Mateeva, Raymonda; Kast, Karin; Deissler, Helmut; Niederacher, Dieter; Arnold, Norbert; Gadzicki, Dorothea; Schönbuchner, Ines; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Dumont, Martine; Chiquette, Jocelyne; Tischkowitz, Marc; Chen, Xiaoqing; Beesley, Jonathan; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan Chun; Fredericksen, Zachary; Wang, Xianshu; Pankratz, Vernon S.; Couch, Fergus; Simard, Jacques; Easton, Douglas F.; Chenevix-Trench, Georgia; Karlsson, Per; Nordling, Margareta; Bergman, Annika; Einbeigi, Zakaria; Stenmark-Askmalm, Marie; Liedgren, Sigrun; Borg, Ake; Loman, Niklas; Olsson, Håkan; Kristoffersson, Ulf; 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.; Veer, L. J van t; 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; Leyland, Jean; Miedzybrodzka, Zosia; Gregory, Helen; Morrison, Patrick; Jeffers, Lisa; Cole, Trevor; McKeown, Carole; Ong, Kai ren; Hoffman, Jonathan; Donaldson, Alan; 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.
In: Human Molecular Genetics, Vol. 20, No. 16, ddr226, 08.2011, p. 3304-3321.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
AU - Antoniou, Antonis C.
AU - Kartsonaki, Christiana
AU - Sinilnikova, Olga M.
AU - Soucy, Penny
AU - McGuffog, Lesley
AU - Healey, Sue
AU - Lee, Andrew
AU - Peterlongo, Paolo
AU - Manoukian, Siranoush
AU - Peissel, Bernard
AU - Zaffaroni, Daniela
AU - Cattaneo, Elisa
AU - Barile, Monica
AU - Pensotti, Valeria
AU - Pasini, Barbara
AU - Dolcetti, Riccardo
AU - Giannini, Giuseppe
AU - Putignano, Anna Laura
AU - Varesco, Liliana
AU - Radice, Paolo
AU - Mai, Phuong L.
AU - Greene, Mark H.
AU - Andrulis, Irene L.
AU - Glendon, Gord
AU - Ozcelik, Hilmi
AU - Thomassen, Mads
AU - Gerdes, Anne Marie
AU - Kruse, Torben A.
AU - Jensen, Uffe Birk
AU - Crüger, Dorthe G.
AU - Caligo, Maria A.
AU - Laitman, Yael
AU - Milgrom, Roni
AU - Kaufman, Bella
AU - Paluch-Shimon, Shani
AU - Friedman, Eitan
AU - Loman, Niklas
AU - Harbst, Katja
AU - Lindblom, Annika
AU - Arver, Brita
AU - Ehrencrona, Hans
AU - Melin, Beatrice
AU - Nathanson, Katherine L.
AU - Domchek, Susan M.
AU - Rebbeck, Timothy
AU - Jakubowska, Ania
AU - Lubinski, Jan
AU - Gronwald, Jacek
AU - Huzarski, Tomasz
AU - Byrski, Tomasz
AU - Cybulski, Cezary
AU - Gorski, Bohdan
AU - Osorio, Ana
AU - Cajal, Teresa Ramón
AU - Fostira, Florentia
AU - Andrés, Raquel
AU - Benitez, Javier
AU - Hamann, Ute
AU - Hogervorst, Frans B.
AU - Rookus, Matti A.
AU - Hooning, Maartje J.
AU - Nelen, Marcel R.
AU - van der Luijt, Rob B.
AU - van Os, Theo A M
AU - van Asperen, Christi J.
AU - Devilee, Peter
AU - Meijers-Heijboer, Hanne E J
AU - Garcia, Encarna B Gómez
AU - Peock, Susan
AU - Cook, Margaret
AU - Frost, D.
AU - Platte, Radka
AU - Leyland, Jean
AU - Evans, D. Gareth
AU - Lalloo, Fiona
AU - Eeles, Ros
AU - Izatt, Louise
AU - Adlard, Julian
AU - Davidson, Rosemarie
AU - Eccles, Diana
AU - Ong, Kai Ren
AU - Cook, Jackie
AU - Douglas, Fiona
AU - Paterson, Joan
AU - Kennedy, M. John
AU - Miedzybrodzka, Zosia
AU - Godwin, Andrew
AU - Stoppa-Lyonnet, Dominique
AU - Buecher, Bruno
AU - Belotti, Muriel
AU - Tirapo, Carole
AU - Mazoyer, Sylvie
AU - Barjhoux, Laure
AU - Lasset, Christine
AU - Leroux, Dominique
AU - Faivre, Laurence
AU - Bronner, Myriam
AU - Prieur, Fabienne
AU - Nogues, Catherine
AU - Rouleau, Etienne
AU - Pujol, Pascal
AU - Coupier, Isabelle
AU - Frénay, Marc
AU - Hopper, John L.
AU - Daly, Mary B.
AU - Terry, Mary B.
AU - John, Esther M.
AU - Buys, Saundra S.
AU - Yassin, Yosuf
AU - Miron, Alexander
AU - Goldgar, David
AU - Singer, Christian F.
AU - Tea, Muy Kheng
AU - Pfeiler, Georg
AU - Dressler, Anne Catharina
AU - Hansen, Thomas v O
AU - Jønson, Lars
AU - Ejlertsen, Bent
AU - Barkardottir, Rosa Bjork
AU - Kirchhoff, Tomas
AU - Offit, Kenneth
AU - Piedmonte, Marion
AU - Rodriguez, Gustavo
AU - Small, Laurie
AU - Boggess, John
AU - Blank, Stephanie
AU - Basil, Jack
AU - Azodi, Masoud
AU - Toland, Amanda Ewart
AU - Montagna, Marco
AU - Tognazzo, Silvia
AU - Agata, Simona
AU - Imyanitov, Evgeny
AU - Janavicius, Ramunas
AU - Lazaro, Conxi
AU - Blanco, Ignacio
AU - Pharoah, Paul D P
AU - Sucheston, Lara
AU - Karlan, Beth Y.
AU - Walsh, Christine S.
AU - Olah, Edith
AU - Bozsik, Aniko
AU - Teo, Soo Hwang
AU - Seldon, Joyce L.
AU - Beattie, Mary S.
AU - van Rensburg, Elizabeth J.
AU - Sluiter, Michelle D.
AU - Diez, Orland
AU - Schmutzler, Rita K.
AU - Wappenschmidt, Barbara
AU - Engel, Christoph
AU - Meindl, Alfons
AU - Ruehl, Ina
AU - Varon-Mateeva, Raymonda
AU - Kast, Karin
AU - Deissler, Helmut
AU - Niederacher, Dieter
AU - Arnold, Norbert
AU - Gadzicki, Dorothea
AU - Schönbuchner, Ines
AU - Caldes, Trinidad
AU - de la Hoya, Miguel
AU - Nevanlinna, Heli
AU - Aittomäki, Kristiina
AU - Dumont, Martine
AU - Chiquette, Jocelyne
AU - Tischkowitz, Marc
AU - Chen, Xiaoqing
AU - Beesley, Jonathan
AU - Spurdle, Amanda B.
AU - Neuhausen, Susan L.
AU - Ding, Yuan Chun
AU - Fredericksen, Zachary
AU - Wang, Xianshu
AU - Pankratz, Vernon S.
AU - Couch, Fergus
AU - Simard, Jacques
AU - Easton, Douglas F.
AU - Chenevix-Trench, Georgia
AU - Karlsson, Per
AU - Nordling, Margareta
AU - Bergman, Annika
AU - Einbeigi, Zakaria
AU - Stenmark-Askmalm, Marie
AU - Liedgren, Sigrun
AU - Borg, Ake
AU - Loman, Niklas
AU - Olsson, Håkan
AU - Kristoffersson, Ulf
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 - Veer, L. J van t
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 - Leyland, Jean
AU - Miedzybrodzka, Zosia
AU - Gregory, Helen
AU - Morrison, Patrick
AU - Jeffers, Lisa
AU - Cole, Trevor
AU - McKeown, Carole
AU - Ong, Kai ren
AU - Hoffman, Jonathan
AU - Donaldson, Alan
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
PY - 2011/8
Y1 - 2011/8
N2 - Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r2 = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 × 10-9 for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10-8 for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
AB - Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r2 = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 × 10-9 for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10-8 for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
UR - http://www.scopus.com/inward/record.url?scp=79960819760&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960819760&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddr226
DO - 10.1093/hmg/ddr226
M3 - Article
C2 - 21593217
AN - SCOPUS:79960819760
VL - 20
SP - 3304
EP - 3321
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 16
M1 - ddr226
ER -