Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

FJ Couch; KB Kuchenbaecker; K Michailidou; GA Mendoza-Fandino; S Nord; J Lilyquist; C Olswold; E Hallberg; S Agata; H Ahsan; K Aittomaki; C Ambrosone; IL Andrulis; H Anton-Culver; V Arndt; BK Arun; B Arver; M Barile; RB Barkardottir; D Barrowdale; L Beckmann; MW Beckmann; J Benitez; SV Blank; C Blomqvist; NV Bogdanova; SE Bojesen; MK Bolla; B Bonanni; H Brauch; H Brenner; B Burwinkel; SS Buys; T Caldes; MA Caligo; F Canzian; J Carpenter; J Chang-Claude; SJ Chanock; WK Chung; KBM Claes; A Cox; SS Cross; JM Cunningham; K Czene; MB Daly; F Damiola; H Darabi; M de la Hoya; P Devilee; O Diez; YC Ding; R Dolcetti; SM Domchek; CM Dorfling; I dos-Santos-Silva; M Dumont; AM Dunning; DM Eccles; H Ehrencrona; AB Ekici; H Eliassen; S Ellis; PA Fasching; J Figueroa; D Flesch-Janys; A Forsti; F Fostira; WD Foulkes; T Friebel; E Friedman; D Frost; M Gabrielson; MD Gammon; PA Ganz; SM Gapstur; J Garber; MM Gaudet; SA Gayther; AM Gerdes; M Ghoussaini; GG Giles; G Glendon; AK Godwin; MS Goldberg; DE Goldgar; A Gonzalez-Neira; MH Greene; J Gronwald; P Guenel; M Gunter; L Haeberle; CA Haiman; U Hamann; TVO Hansen; S Hart; S Healey; T Heikkinen; BE Henderson; J Herzog; FBL Hogervorst; Antoinette Hollestelle; Maartje Hooning; RN Hoover; JL Hopper; K Humphreys; DJ Hunter; T Huzarski; EN Imyanitov; C Isaacs; A Jakubowska; P James; R Janavicius; UB Jensen; EM John; M Jones; M Kabisch; S Kar; BY Karlan; Salima Khan; KT Khaw; MG Kibriya; JA Knight; YD Ko; I Konstantopoulou; VM Kosma; V Kristensen; A Kwong; Y Laitman; D Lambrechts; C (Conxi) Lazaro; E Lee; L Le Marchand; J Lester; A Lindblom; N Lindor; S Lindstrom; J (Jingjing) Liu; J Long; J Lubinski; PL Mai; E Makalic; KE Malone; A Mannermaa; S Manoukian; S Margolin; F Marme; John Martens; L McGuffog; A Meindl; A Miller; RL Milne; P Miron; M Montagna; S Mazoyer; AM Mulligan; TA Muranen; KL Nathanson; SL Neuhausen; H Nevanlinna; BG Nordestgaard; RL Nussbaum; K Offit; E Olah; OI Olopade; JE Olson; A Osorio; SK Park; PH Peeters; B Peissel; P Peterlongo; J Peto; CM Phelan; R Pilarski; B (Bruce) Poppe; K Pylkas; P Radice; N Rahman; J Rantala; C Rappaport; G Rennert; A Richardson; M Robson; I Romieu; A Rudolph; EJ Rutgers; MJ (Maria-Jose) Sanchez; RM Santella; EJ Sawyer; DF Schmidt; MK (Marjanka) Schmidt; RK Schmutzler; F Schumacher; R Scott; L Senter; P Sharma; J Simard; CF Singer; OM Sinilnikova; P Soucy; M Southey; D Steinemann; M Stenmark-Askmalm; D Stoppa-Lyonnet; A Swerdlow; CI Szabo; R Tamimi; W Tapper; MR Teixeira; SH Teo; MB Terry; M Thomassen; D Thompson; L Tihomirova; AE Toland; RAEM Tollenaar; I Tomlinson; T Truong; H Tsimiklis; A Teule; R Tumino; N Tung; C Turnbull; G Ursin; Carolien van Deurzen; EJ van Rensburg; R Varon-Mateeva; ZM Wang; S Wang-Gohrke; E Weiderpass; JN Weitzel; A Whittemore; H Wildiers; R Winqvist; XHR Yang; D Yannoukakos; S Yao; MP Zamora; W Zheng; P Hall; P Kraft; C Vachon; S Slager; G Chenevix-Trench; PDP Pharoah; AAN Monteiro; M Garcia-Closas; DF Easton; AC Antoniou

doi:10.1038/ncomms11375

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

FJ Couch
, KB Kuchenbaecker
, K Michailidou
, GA Mendoza-Fandino
, S Nord
, J Lilyquist
, C Olswold
, E Hallberg
, S Agata
, H Ahsan
, K Aittomaki
, C Ambrosone
, IL Andrulis
, H Anton-Culver
, V Arndt
, BK Arun
, B Arver
, M Barile
, RB Barkardottir
, D Barrowdale

L Beckmann, MW Beckmann, J Benitez, SV Blank, C Blomqvist, NV Bogdanova, SE Bojesen, MK Bolla, B Bonanni, H Brauch, H Brenner, B Burwinkel, SS Buys, T Caldes, MA Caligo, F Canzian, J Carpenter, J Chang-Claude, SJ Chanock, WK Chung, KBM Claes, A Cox, SS Cross, JM Cunningham, K Czene, MB Daly, F Damiola, H Darabi, M de la Hoya, P Devilee, O Diez, YC Ding, R Dolcetti, SM Domchek, CM Dorfling, I dos-Santos-Silva, M Dumont, AM Dunning, DM Eccles, H Ehrencrona, AB Ekici, H Eliassen, S Ellis, PA Fasching, J Figueroa, D Flesch-Janys, A Forsti, F Fostira, WD Foulkes, T Friebel, E Friedman, D Frost, M Gabrielson, MD Gammon, PA Ganz, SM Gapstur, J Garber, MM Gaudet, SA Gayther, AM Gerdes, M Ghoussaini, GG Giles, G Glendon, AK Godwin, MS Goldberg, DE Goldgar, A Gonzalez-Neira, MH Greene, J Gronwald, P Guenel, M Gunter, L Haeberle, CA Haiman, U Hamann, TVO Hansen, S Hart, S Healey, T Heikkinen, BE Henderson, J Herzog, FBL Hogervorst, Antoinette Hollestelle, Maartje Hooning, RN Hoover, JL Hopper, K Humphreys, DJ Hunter, T Huzarski, EN Imyanitov, C Isaacs, A Jakubowska, P James, R Janavicius, UB Jensen, EM John, M Jones, M Kabisch, S Kar, BY Karlan, Salima Khan, KT Khaw, MG Kibriya, JA Knight, YD Ko, I Konstantopoulou, VM Kosma, V Kristensen, A Kwong, Y Laitman, D Lambrechts, C (Conxi) Lazaro, E Lee, L Le Marchand, J Lester, A Lindblom, N Lindor, S Lindstrom, J (Jingjing) Liu, J Long, J Lubinski, PL Mai, E Makalic, KE Malone, A Mannermaa, S Manoukian, S Margolin, F Marme, John Martens, L McGuffog, A Meindl, A Miller, RL Milne, P Miron, M Montagna, S Mazoyer, AM Mulligan, TA Muranen, KL Nathanson, SL Neuhausen, H Nevanlinna, BG Nordestgaard, RL Nussbaum, K Offit, E Olah, OI Olopade, JE Olson, A Osorio, SK Park, PH Peeters, B Peissel, P Peterlongo, J Peto, CM Phelan, R Pilarski, B (Bruce) Poppe, K Pylkas, P Radice, N Rahman, J Rantala, C Rappaport, G Rennert, A Richardson, M Robson, I Romieu, A Rudolph, EJ Rutgers, MJ (Maria-Jose) Sanchez, RM Santella, EJ Sawyer, DF Schmidt, MK (Marjanka) Schmidt, RK Schmutzler, F Schumacher, R Scott, L Senter, P Sharma, J Simard, CF Singer, OM Sinilnikova, P Soucy, M Southey, D Steinemann, M Stenmark-Askmalm, D Stoppa-Lyonnet, A Swerdlow, CI Szabo, R Tamimi, W Tapper, MR Teixeira, SH Teo, MB Terry, M Thomassen, D Thompson, L Tihomirova, AE Toland, RAEM Tollenaar, I Tomlinson, T Truong, H Tsimiklis, A Teule, R Tumino, N Tung, C Turnbull, G Ursin, Carolien van Deurzen, EJ van Rensburg, R Varon-Mateeva, ZM Wang, S Wang-Gohrke, E Weiderpass, JN Weitzel, A Whittemore, H Wildiers, R Winqvist, XHR Yang, D Yannoukakos, S Yao, MP Zamora, W Zheng, P Hall, P Kraft, C Vachon, S Slager, G Chenevix-Trench, PDP Pharoah, AAN Monteiro, M Garcia-Closas, DF Easton, AC Antoniou

External organisation

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

88 Citations (Scopus)

34 Downloads (Pure)

Abstract

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

Original language	Undefined/Unknown
Article number	11375
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11375
Publication status	Published - 2016

Research programs

EMC MM-03-24-01
EMC MM-03-86-01

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ncomms11375

REPUB_81552-OA.pdfFinal published version, 0.99 MB

http://hdl.handle.net/1765/81552

Cite this

Couch, FJ., Kuchenbaecker, KB., Michailidou, K., Mendoza-Fandino, GA., Nord, S., Lilyquist, J., Olswold, C., Hallberg, E., Agata, S., Ahsan, H., Aittomaki, K., Ambrosone, C., Andrulis, IL., Anton-Culver, H., Arndt, V., Arun, BK., Arver, B., Barile, M., Barkardottir, RB., ... Antoniou, AC. (2016). Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer. Nature Communications, 7, Article 11375. https://doi.org/10.1038/ncomms11375

@article{f590e4dbf03c4078b68be8d79634e5ed,

title = "Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer",

abstract = "Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11\% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.",

author = "FJ Couch and KB Kuchenbaecker and K Michailidou and GA Mendoza-Fandino and S Nord and J Lilyquist and C Olswold and E Hallberg and S Agata and H Ahsan and K Aittomaki and C Ambrosone and IL Andrulis and H Anton-Culver and V Arndt and BK Arun and B Arver and M Barile and RB Barkardottir and D Barrowdale and L Beckmann and MW Beckmann and J Benitez and SV Blank and C Blomqvist and NV Bogdanova and SE Bojesen and MK Bolla and B Bonanni and H Brauch and H Brenner and B Burwinkel and SS Buys and T Caldes and MA Caligo and F Canzian and J Carpenter and J Chang-Claude and SJ Chanock and WK Chung and KBM Claes and A Cox and SS Cross and JM Cunningham and K Czene and MB Daly and F Damiola and H Darabi and \{de la Hoya\}, M and P Devilee and O Diez and YC Ding and R Dolcetti and SM Domchek and CM Dorfling and I dos-Santos-Silva and M Dumont and AM Dunning and DM Eccles and H Ehrencrona and AB Ekici and H Eliassen and S Ellis and PA Fasching and J Figueroa and D Flesch-Janys and A Forsti and F Fostira and WD Foulkes and T Friebel and E Friedman and D Frost and M Gabrielson and MD Gammon and PA Ganz and SM Gapstur and J Garber and MM Gaudet and SA Gayther and AM Gerdes and M Ghoussaini and GG Giles and G Glendon and AK Godwin and MS Goldberg and DE Goldgar and A Gonzalez-Neira and MH Greene and J Gronwald and P Guenel and M Gunter and L Haeberle and CA Haiman and U Hamann and TVO Hansen and S Hart and S Healey and T Heikkinen and BE Henderson and J Herzog and FBL Hogervorst and Antoinette Hollestelle and Maartje Hooning and RN Hoover and JL Hopper and K Humphreys and DJ Hunter and T Huzarski and EN Imyanitov and C Isaacs and A Jakubowska and P James and R Janavicius and UB Jensen and EM John and M Jones and M Kabisch and S Kar and BY Karlan and Salima Khan and KT Khaw and MG Kibriya and JA Knight and YD Ko and I Konstantopoulou and VM Kosma and V Kristensen and A Kwong and Y Laitman and D Lambrechts and Lazaro, \{C (Conxi)\} and E Lee and \{Le Marchand\}, L and J Lester and A Lindblom and N Lindor and S Lindstrom and Liu, \{J (Jingjing)\} and J Long and J Lubinski and PL Mai and E Makalic and KE Malone and A Mannermaa and S Manoukian and S Margolin and F Marme and John Martens and L McGuffog and A Meindl and A Miller and RL Milne and P Miron and M Montagna and S Mazoyer and AM Mulligan and TA Muranen and KL Nathanson and SL Neuhausen and H Nevanlinna and BG Nordestgaard and RL Nussbaum and K Offit and E Olah and OI Olopade and JE Olson and A Osorio and SK Park and PH Peeters and B Peissel and P Peterlongo and J Peto and CM Phelan and R Pilarski and Poppe, \{B (Bruce)\} and K Pylkas and P Radice and N Rahman and J Rantala and C Rappaport and G Rennert and A Richardson and M Robson and I Romieu and A Rudolph and EJ Rutgers and Sanchez, \{MJ (Maria-Jose)\} and RM Santella and EJ Sawyer and DF Schmidt and Schmidt, \{MK (Marjanka)\} and RK Schmutzler and F Schumacher and R Scott and L Senter and P Sharma and J Simard and CF Singer and OM Sinilnikova and P Soucy and M Southey and D Steinemann and M Stenmark-Askmalm and D Stoppa-Lyonnet and A Swerdlow and CI Szabo and R Tamimi and W Tapper and MR Teixeira and SH Teo and MB Terry and M Thomassen and D Thompson and L Tihomirova and AE Toland and RAEM Tollenaar and I Tomlinson and T Truong and H Tsimiklis and A Teule and R Tumino and N Tung and C Turnbull and G Ursin and \{van Deurzen\}, Carolien and \{van Rensburg\}, EJ and R Varon-Mateeva and ZM Wang and S Wang-Gohrke and E Weiderpass and JN Weitzel and A Whittemore and H Wildiers and R Winqvist and XHR Yang and D Yannoukakos and S Yao and MP Zamora and W Zheng and P Hall and P Kraft and C Vachon and S Slager and G Chenevix-Trench and PDP Pharoah and AAN Monteiro and M Garcia-Closas and DF Easton and AC Antoniou",

year = "2016",

doi = "10.1038/ncomms11375",

language = "Undefined/Unknown",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

Couch, FJ, Kuchenbaecker, KB, Michailidou, K, Mendoza-Fandino, GA, Nord, S, Lilyquist, J, Olswold, C, Hallberg, E, Agata, S, Ahsan, H, Aittomaki, K, Ambrosone, C, Andrulis, IL, Anton-Culver, H, Arndt, V, Arun, BK, Arver, B, Barile, M, Barkardottir, RB, Barrowdale, D, Beckmann, L, Beckmann, MW, Benitez, J, Blank, SV, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldes, T, Caligo, MA, Canzian, F, Carpenter, J, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Cox, A, Cross, SS, Cunningham, JM, Czene, K, Daly, MB, Damiola, F, Darabi, H, de la Hoya, M, Devilee, P, Diez, O, Ding, YC, Dolcetti, R, Domchek, SM, Dorfling, CM, dos-Santos-Silva, I, Dumont, M, Dunning, AM, Eccles, DM, Ehrencrona, H, Ekici, AB, Eliassen, H, Ellis, S, Fasching, PA, Figueroa, J, Flesch-Janys, D, Forsti, A, Fostira, F, Foulkes, WD, Friebel, T, Friedman, E, Frost, D, Gabrielson, M, Gammon, MD, Ganz, PA, Gapstur, SM, Garber, J, Gaudet, MM, Gayther, SA, Gerdes, AM, Ghoussaini, M, Giles, GG, Glendon, G, Godwin, AK, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Greene, MH, Gronwald, J, Guenel, P, Gunter, M, Haeberle, L, Haiman, CA, Hamann, U, Hansen, TVO, Hart, S, Healey, S, Heikkinen, T, Henderson, BE, Herzog, J, Hogervorst, FBL, Hollestelle, A, Hooning, M, Hoover, RN, Hopper, JL, Humphreys, K, Hunter, DJ, Huzarski, T, Imyanitov, EN, Isaacs, C, Jakubowska, A, James, P, Janavicius, R, Jensen, UB, John, EM, Jones, M, Kabisch, M, Kar, S, Karlan, BY, Khan, S, Khaw, KT, Kibriya, MG, Knight, JA, Ko, YD, Konstantopoulou, I, Kosma, VM, Kristensen, V, Kwong, A, Laitman, Y, Lambrechts, D, Lazaro, C, Lee, E, Le Marchand, L, Lester, J, Lindblom, A, Lindor, N, Lindstrom, S, Liu, J, Long, J, Lubinski, J, Mai, PL, Makalic, E, Malone, KE, Mannermaa, A, Manoukian, S, Margolin, S, Marme, F, Martens, J, McGuffog, L, Meindl, A, Miller, A, Milne, RL, Miron, P, Montagna, M, Mazoyer, S, Mulligan, AM, Muranen, TA, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nordestgaard, BG, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Olson, JE, Osorio, A, Park, SK, Peeters, PH, Peissel, B, Peterlongo, P, Peto, J, Phelan, CM, Pilarski, R, Poppe, B, Pylkas, K, Radice, P, Rahman, N, Rantala, J, Rappaport, C, Rennert, G, Richardson, A, Robson, M, Romieu, I, Rudolph, A, Rutgers, EJ, Sanchez, MJ, Santella, RM, Sawyer, EJ, Schmidt, DF, Schmidt, MK, Schmutzler, RK, Schumacher, F, Scott, R, Senter, L, Sharma, P, Simard, J, Singer, CF, Sinilnikova, OM, Soucy, P, Southey, M, Steinemann, D, Stenmark-Askmalm, M, Stoppa-Lyonnet, D, Swerdlow, A, Szabo, CI, Tamimi, R, Tapper, W, Teixeira, MR, Teo, SH, Terry, MB, Thomassen, M, Thompson, D, Tihomirova, L, Toland, AE, Tollenaar, RAEM, Tomlinson, I, Truong, T, Tsimiklis, H, Teule, A, Tumino, R, Tung, N, Turnbull, C, Ursin, G, van Deurzen, C, van Rensburg, EJ, Varon-Mateeva, R, Wang, ZM, Wang-Gohrke, S, Weiderpass, E, Weitzel, JN, Whittemore, A, Wildiers, H, Winqvist, R, Yang, XHR, Yannoukakos, D, Yao, S, Zamora, MP, Zheng, W, Hall, P, Kraft, P, Vachon, C, Slager, S, Chenevix-Trench, G, Pharoah, PDP, Monteiro, AAN, Garcia-Closas, M, Easton, DF & Antoniou, AC 2016, 'Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer', Nature Communications, vol. 7, 11375. https://doi.org/10.1038/ncomms11375

TY - JOUR

T1 - Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

AU - Couch, FJ

AU - Kuchenbaecker, KB

AU - Michailidou, K

AU - Mendoza-Fandino, GA

AU - Nord, S

AU - Lilyquist, J

AU - Olswold, C

AU - Hallberg, E

AU - Agata, S

AU - Ahsan, H

AU - Aittomaki, K

AU - Ambrosone, C

AU - Andrulis, IL

AU - Anton-Culver, H

AU - Arndt, V

AU - Arun, BK

AU - Arver, B

AU - Barile, M

AU - Barkardottir, RB

AU - Barrowdale, D

AU - Beckmann, L

AU - Beckmann, MW

AU - Benitez, J

AU - Blank, SV

AU - Blomqvist, C

AU - Bogdanova, NV

AU - Bojesen, SE

AU - Bolla, MK

AU - Bonanni, B

AU - Brauch, H

AU - Brenner, H

AU - Burwinkel, B

AU - Buys, SS

AU - Caldes, T

AU - Caligo, MA

AU - Canzian, F

AU - Carpenter, J

AU - Chang-Claude, J

AU - Chanock, SJ

AU - Chung, WK

AU - Claes, KBM

AU - Cox, A

AU - Cross, SS

AU - Cunningham, JM

AU - Czene, K

AU - Daly, MB

AU - Damiola, F

AU - Darabi, H

AU - de la Hoya, M

AU - Devilee, P

AU - Diez, O

AU - Ding, YC

AU - Dolcetti, R

AU - Domchek, SM

AU - Dorfling, CM

AU - dos-Santos-Silva, I

AU - Dumont, M

AU - Dunning, AM

AU - Eccles, DM

AU - Ehrencrona, H

AU - Ekici, AB

AU - Eliassen, H

AU - Ellis, S

AU - Fasching, PA

AU - Figueroa, J

AU - Flesch-Janys, D

AU - Forsti, A

AU - Fostira, F

AU - Foulkes, WD

AU - Friebel, T

AU - Friedman, E

AU - Frost, D

AU - Gabrielson, M

AU - Gammon, MD

AU - Ganz, PA

AU - Gapstur, SM

AU - Garber, J

AU - Gaudet, MM

AU - Gayther, SA

AU - Gerdes, AM

AU - Ghoussaini, M

AU - Giles, GG

AU - Glendon, G

AU - Godwin, AK

AU - Goldberg, MS

AU - Goldgar, DE

AU - Gonzalez-Neira, A

AU - Greene, MH

AU - Gronwald, J

AU - Guenel, P

AU - Gunter, M

AU - Haeberle, L

AU - Haiman, CA

AU - Hamann, U

AU - Hansen, TVO

AU - Hart, S

AU - Healey, S

AU - Heikkinen, T

AU - Henderson, BE

AU - Herzog, J

AU - Hogervorst, FBL

AU - Hollestelle, Antoinette

AU - Hooning, Maartje

AU - Hoover, RN

AU - Hopper, JL

AU - Humphreys, K

AU - Hunter, DJ

AU - Huzarski, T

AU - Imyanitov, EN

AU - Isaacs, C

AU - Jakubowska, A

AU - James, P

AU - Janavicius, R

AU - Jensen, UB

AU - John, EM

AU - Jones, M

AU - Kabisch, M

AU - Kar, S

AU - Karlan, BY

AU - Khan, Salima

AU - Khaw, KT

AU - Kibriya, MG

AU - Knight, JA

AU - Ko, YD

AU - Konstantopoulou, I

AU - Kosma, VM

AU - Kristensen, V

AU - Kwong, A

AU - Laitman, Y

AU - Lambrechts, D

AU - Lazaro, C (Conxi)

AU - Lee, E

AU - Le Marchand, L

AU - Lester, J

AU - Lindblom, A

AU - Lindor, N

AU - Lindstrom, S

AU - Liu, J (Jingjing)

AU - Long, J

AU - Lubinski, J

AU - Mai, PL

AU - Makalic, E

AU - Malone, KE

AU - Mannermaa, A

AU - Manoukian, S

AU - Margolin, S

AU - Marme, F

AU - Martens, John

AU - McGuffog, L

AU - Meindl, A

AU - Miller, A

AU - Milne, RL

AU - Miron, P

AU - Montagna, M

AU - Mazoyer, S

AU - Mulligan, AM

AU - Muranen, TA

AU - Nathanson, KL

AU - Neuhausen, SL

AU - Nevanlinna, H

AU - Nordestgaard, BG

AU - Nussbaum, RL

AU - Offit, K

AU - Olah, E

AU - Olopade, OI

AU - Olson, JE

AU - Osorio, A

AU - Park, SK

AU - Peeters, PH

AU - Peissel, B

AU - Peterlongo, P

AU - Peto, J

AU - Phelan, CM

AU - Pilarski, R

AU - Poppe, B (Bruce)

AU - Pylkas, K

AU - Radice, P

AU - Rahman, N

AU - Rantala, J

AU - Rappaport, C

AU - Rennert, G

AU - Richardson, A

AU - Robson, M

AU - Romieu, I

AU - Rudolph, A

AU - Rutgers, EJ

AU - Sanchez, MJ (Maria-Jose)

AU - Santella, RM

AU - Sawyer, EJ

AU - Schmidt, DF

AU - Schmidt, MK (Marjanka)

AU - Schmutzler, RK

AU - Schumacher, F

AU - Scott, R

AU - Senter, L

AU - Sharma, P

AU - Simard, J

AU - Singer, CF

AU - Sinilnikova, OM

AU - Soucy, P

AU - Southey, M

AU - Steinemann, D

AU - Stenmark-Askmalm, M

AU - Stoppa-Lyonnet, D

AU - Swerdlow, A

AU - Szabo, CI

AU - Tamimi, R

AU - Tapper, W

AU - Teixeira, MR

AU - Teo, SH

AU - Terry, MB

AU - Thomassen, M

AU - Thompson, D

AU - Tihomirova, L

AU - Toland, AE

AU - Tollenaar, RAEM

AU - Tomlinson, I

AU - Truong, T

AU - Tsimiklis, H

AU - Teule, A

AU - Tumino, R

AU - Tung, N

AU - Turnbull, C

AU - Ursin, G

AU - van Deurzen, Carolien

AU - van Rensburg, EJ

AU - Varon-Mateeva, R

AU - Wang, ZM

AU - Wang-Gohrke, S

AU - Weiderpass, E

AU - Weitzel, JN

AU - Whittemore, A

AU - Wildiers, H

AU - Winqvist, R

AU - Yang, XHR

AU - Yannoukakos, D

AU - Yao, S

AU - Zamora, MP

AU - Zheng, W

AU - Hall, P

AU - Kraft, P

AU - Vachon, C

AU - Slager, S

AU - Chenevix-Trench, G

AU - Pharoah, PDP

AU - Monteiro, AAN

AU - Garcia-Closas, M

AU - Easton, DF

AU - Antoniou, AC

PY - 2016

Y1 - 2016

N2 - Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

AB - Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

U2 - 10.1038/ncomms11375

DO - 10.1038/ncomms11375

M3 - Article

C2 - 27117709

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11375

ER -