Genome-wide association analysis identifies three new breast cancer susceptibility loci

M Ghoussaini; O Fletcher; K Michailidou; C Turnbull; Marjanka K Schmidt; E Dicks; J Dennis; Q (Qing) Wang; MK Humphreys; C Luccarini; C Baynes; D Conroy; M Maranian; S (Shahana) Ahmed; K Driver; N Johnson; N Orr; ID Silva; Q Waisfisz; H Meijers-Heijboer; André Uitterlinden; Fernando Rivadeneira; P Hall; K Czene; A Irwanto; JJ Liu; H Nevanlinna; K Aittomaki; C Blomqvist; A Meindl; RK Schmutzler; B Muller-Myhsok; P Lichtner; J Chang-Claude; R Hein; S Nickels; D Flesch-Janys; H Tsimiklis; E Makalic; D Schmidt; M Bui; JL Hopper; C Apicella; DJ Park; M Southey; DJ Hunter; SJ Chanock; A Broeks; S Verhoef; FBL Hogervorst; PA Fasching; MP Lux; MW Beckmann; AB Ekici; E Sawyer; I Tomlinson; M Kerin; F Marme; A Schneeweiss; C Sohn; B Burwinkel; P Guenal; T Truong; E Cordina-Duverger; F Menegaux; SE Bojesen; BG Nordestgaard; SF Nielsen; H Flyger; RL Milne; MR Alonso; A Gonzalez-Neira; J Benitez; H Anton-Culver; A Ziogas; L Bernstein; CC Dur; H Brenner; H Muller; V Arndt; C Stegmaier; C Justenhoven; H Brauch; T Bruning; S Wang-Gohrke; U Eilber; T Dork; P Schurmann; M Bremer; P Hillemanns; NV Bogdanova; NN Antonenkova; YI Rogov; JH Karstens; M Bermisheva; D Prokofieva; E Khusnutdinova; A Lindblom; S Margolin; A Mannermaa; V Kataja; VM Kosma; JM Hartikainen; D Lambrechts; BT Yesilyurt; G Floris; K Leunen; S Manoukian; B Bonanni; S Fortuzzi; P Peterlongo; FJ Couch; XS Wang; K Stevens; A Lee; GG Giles; L Baglietto; G Severi; C McLean; GG Alnaes; V Kristensen; AL Borrensen-Dale; EM John; A Miron; R Winqvist; K Pylkas; A Jukkola-Vuorinen; S Kauppila; IL Andrulis; G Glendon; AM Mulligan; P Devilee; CJ van Asperen; RAEM Tollenaar; Caroline Seynaeve; JD Figueroa; M Garcia-Closas; L Brinton; J Lissowska; Maartje Hooning; Antoinette Hollestelle; Rogier Oldenburg; Ans van den Ouweland; A Cox; MWR Reed; M Shah; A Jakubowska; J Lubinski; K Jaworska; K Durda; M Jones; M Schoemaker; A Ashworth; A Swerdlow; J Beesley; XQ Chen; KR Muir; A Lophatananon; S Rattanamongkongul; A Chaiwerawattana; D Kang; KY Yoo; DY Noh; CY Shen; JC Yu; PE Wu; CN Hsiung; A Perkins; R Swann; L Velentzis; DM Eccles; WJ Tapper; SM Gerty; NJ Graham; BAJ Ponder; G Chenevix-Trench; PDP Pharoah; M Lathrop; AM Dunning; N Rahman; J Peto; DF Easton

doi:10.1038/ng.1049

Genome-wide association analysis identifies three new breast cancer susceptibility loci

M Ghoussaini, O Fletcher, K Michailidou, C Turnbull, Marjanka K Schmidt, E Dicks, J Dennis, Q (Qing) Wang, MK Humphreys, C Luccarini, C Baynes, D Conroy, M Maranian, S (Shahana) Ahmed, K Driver, N Johnson, N Orr, ID Silva, Q Waisfisz, H Meijers-HeijboerAndré Uitterlinden, Fernando Rivadeneira, P Hall, K Czene, A Irwanto, JJ Liu, H Nevanlinna, K Aittomaki, C Blomqvist, A Meindl, RK Schmutzler, B Muller-Myhsok, P Lichtner, J Chang-Claude, R Hein, S Nickels, D Flesch-Janys, H Tsimiklis, E Makalic, D Schmidt, M Bui, JL Hopper, C Apicella, DJ Park, M Southey, DJ Hunter, SJ Chanock, A Broeks, S Verhoef, FBL Hogervorst, PA Fasching, MP Lux, MW Beckmann, AB Ekici, E Sawyer, I Tomlinson, M Kerin, F Marme, A Schneeweiss, C Sohn, B Burwinkel, P Guenal, T Truong, E Cordina-Duverger, F Menegaux, SE Bojesen, BG Nordestgaard, SF Nielsen, H Flyger, RL Milne, MR Alonso, A Gonzalez-Neira, J Benitez, H Anton-Culver, A Ziogas, L Bernstein, CC Dur, H Brenner, H Muller, V Arndt, C Stegmaier, C Justenhoven, H Brauch, T Bruning, S Wang-Gohrke, U Eilber, T Dork, P Schurmann, M Bremer, P Hillemanns, NV Bogdanova, NN Antonenkova, YI Rogov, JH Karstens, M Bermisheva, D Prokofieva, E Khusnutdinova, A Lindblom, S Margolin, A Mannermaa, V Kataja, VM Kosma, JM Hartikainen, D Lambrechts, BT Yesilyurt, G Floris, K Leunen, S Manoukian, B Bonanni, S Fortuzzi, P Peterlongo, FJ Couch, XS Wang, K Stevens, A Lee, GG Giles, L Baglietto, G Severi, C McLean, GG Alnaes, V Kristensen, AL Borrensen-Dale, EM John, A Miron, R Winqvist, K Pylkas, A Jukkola-Vuorinen, S Kauppila, IL Andrulis, G Glendon, AM Mulligan, P Devilee, CJ van Asperen, RAEM Tollenaar, Caroline Seynaeve, JD Figueroa, M Garcia-Closas, L Brinton, J Lissowska, Maartje Hooning, Antoinette Hollestelle, Rogier Oldenburg, Ans van den Ouweland, A Cox, MWR Reed, M Shah, A Jakubowska, J Lubinski, K Jaworska, K Durda, M Jones, M Schoemaker, A Ashworth, A Swerdlow, J Beesley, XQ Chen, KR Muir, A Lophatananon, S Rattanamongkongul, A Chaiwerawattana, D Kang, KY Yoo, DY Noh, CY Shen, JC Yu, PE Wu, CN Hsiung, A Perkins, R Swann, L Velentzis, DM Eccles, WJ Tapper, SM Gerty, NJ Graham, BAJ Ponder, G Chenevix-Trench, PDP Pharoah, M Lathrop, AM Dunning, N Rahman, J Peto, DF Easton

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

239 Citations (Scopus)

Abstract

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for similar to 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in similar to 70,000 cases and similar to 68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 x 10(-35)), 12q24 (rs1292011; P = 4.3 x 10(-19)) and 21q21 (rs2823093; P = 1.1 x 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.

Original language	Undefined/Unknown
Pages (from-to)	312-U120
Journal	Nature Genetics
Volume	44
Issue number	3
DOIs	https://doi.org/10.1038/ng.1049
Publication status	Published - 2012

Research programs

EMC MGC-02-96-01
EMC MM-01-39-09-A
EMC MM-03-86-01

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

Access to Document

10.1038/ng.1049

http://hdl.handle.net/1765/56759

Cite this

Ghoussaini, M., Fletcher, O., Michailidou, K., Turnbull, C., Schmidt, M. K., Dicks, E., Dennis, J., Wang, Q., Humphreys, MK., Luccarini, C., Baynes, C., Conroy, D., Maranian, M., Ahmed, S., Driver, K., Johnson, N., Orr, N., Silva, ID., Waisfisz, Q., ... Easton, DF. (2012). Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nature Genetics, 44(3), 312-U120. https://doi.org/10.1038/ng.1049

@article{b48c2687c8d04f5cae99a21276f73aac,

title = "Genome-wide association analysis identifies three new breast cancer susceptibility loci",

abstract = "Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for similar to 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in similar to 70,000 cases and similar to 68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 x 10(-35)), 12q24 (rs1292011; P = 4.3 x 10(-19)) and 21q21 (rs2823093; P = 1.1 x 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.",

author = "M Ghoussaini and O Fletcher and K Michailidou and C Turnbull and Schmidt, {Marjanka K} and E Dicks and J Dennis and Wang, {Q (Qing)} and MK Humphreys and C Luccarini and C Baynes and D Conroy and M Maranian and Ahmed, {S (Shahana)} and K Driver and N Johnson and N Orr and ID Silva and Q Waisfisz and H Meijers-Heijboer and Andr{\'e} Uitterlinden and Fernando Rivadeneira and P Hall and K Czene and A Irwanto and JJ Liu and H Nevanlinna and K Aittomaki and C Blomqvist and A Meindl and RK Schmutzler and B Muller-Myhsok and P Lichtner and J Chang-Claude and R Hein and S Nickels and D Flesch-Janys and H Tsimiklis and E Makalic and D Schmidt and M Bui and JL Hopper and C Apicella and DJ Park and M Southey and DJ Hunter and SJ Chanock and A Broeks and S Verhoef and FBL Hogervorst and PA Fasching and MP Lux and MW Beckmann and AB Ekici and E Sawyer and I Tomlinson and M Kerin and F Marme and A Schneeweiss and C Sohn and B Burwinkel and P Guenal and T Truong and E Cordina-Duverger and F Menegaux and SE Bojesen and BG Nordestgaard and SF Nielsen and H Flyger and RL Milne and MR Alonso and A Gonzalez-Neira and J Benitez and H Anton-Culver and A Ziogas and L Bernstein and CC Dur and H Brenner and H Muller and V Arndt and C Stegmaier and C Justenhoven and H Brauch and T Bruning and S Wang-Gohrke and U Eilber and T Dork and P Schurmann and M Bremer and P Hillemanns and NV Bogdanova and NN Antonenkova and YI Rogov and JH Karstens and M Bermisheva and D Prokofieva and E Khusnutdinova and A Lindblom and S Margolin and A Mannermaa and V Kataja and VM Kosma and JM Hartikainen and D Lambrechts and BT Yesilyurt and G Floris and K Leunen and S Manoukian and B Bonanni and S Fortuzzi and P Peterlongo and FJ Couch and XS Wang and K Stevens and A Lee and GG Giles and L Baglietto and G Severi and C McLean and GG Alnaes and V Kristensen and AL Borrensen-Dale and EM John and A Miron and R Winqvist and K Pylkas and A Jukkola-Vuorinen and S Kauppila and IL Andrulis and G Glendon and AM Mulligan and P Devilee and {van Asperen}, CJ and RAEM Tollenaar and Caroline Seynaeve and JD Figueroa and M Garcia-Closas and L Brinton and J Lissowska and Maartje Hooning and Antoinette Hollestelle and Rogier Oldenburg and {van den Ouweland}, Ans and A Cox and MWR Reed and M Shah and A Jakubowska and J Lubinski and K Jaworska and K Durda and M Jones and M Schoemaker and A Ashworth and A Swerdlow and J Beesley and XQ Chen and KR Muir and A Lophatananon and S Rattanamongkongul and A Chaiwerawattana and D Kang and KY Yoo and DY Noh and CY Shen and JC Yu and PE Wu and CN Hsiung and A Perkins and R Swann and L Velentzis and DM Eccles and WJ Tapper and SM Gerty and NJ Graham and BAJ Ponder and G Chenevix-Trench and PDP Pharoah and M Lathrop and AM Dunning and N Rahman and J Peto and DF Easton",

year = "2012",

doi = "10.1038/ng.1049",

language = "Undefined/Unknown",

volume = "44",

pages = "312--U120",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "3",

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Ghoussaini, M, Fletcher, O, Michailidou, K, Turnbull, C, Schmidt, MK, Dicks, E, Dennis, J, Wang, Q, Humphreys, MK, Luccarini, C, Baynes, C, Conroy, D, Maranian, M, Ahmed, S, Driver, K, Johnson, N, Orr, N, Silva, ID, Waisfisz, Q, Meijers-Heijboer, H, Uitterlinden, A , Rivadeneira, F, Hall, P, Czene, K, Irwanto, A, Liu, JJ, Nevanlinna, H, Aittomaki, K, Blomqvist, C, Meindl, A, Schmutzler, RK, Muller-Myhsok, B, Lichtner, P, Chang-Claude, J, Hein, R, Nickels, S, Flesch-Janys, D, Tsimiklis, H, Makalic, E, Schmidt, D, Bui, M, Hopper, JL, Apicella, C, Park, DJ, Southey, M, Hunter, DJ, Chanock, SJ, Broeks, A, Verhoef, S, Hogervorst, FBL, Fasching, PA, Lux, MP, Beckmann, MW, Ekici, AB, Sawyer, E, Tomlinson, I, Kerin, M, Marme, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guenal, P, Truong, T, Cordina-Duverger, E, Menegaux, F, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, Milne, RL, Alonso, MR, Gonzalez-Neira, A, Benitez, J, Anton-Culver, H, Ziogas, A, Bernstein, L, Dur, CC, Brenner, H, Muller, H, Arndt, V, Stegmaier, C, Justenhoven, C, Brauch, H, Bruning, T, Wang-Gohrke, S, Eilber, U, Dork, T, Schurmann, P, Bremer, M, Hillemanns, P, Bogdanova, NV, Antonenkova, NN, Rogov, YI, Karstens, JH, Bermisheva, M, Prokofieva, D, Khusnutdinova, E, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, JM, Lambrechts, D, Yesilyurt, BT, Floris, G, Leunen, K, Manoukian, S, Bonanni, B, Fortuzzi, S, Peterlongo, P, Couch, FJ, Wang, XS, Stevens, K, Lee, A, Giles, GG, Baglietto, L, Severi, G, McLean, C, Alnaes, GG, Kristensen, V, Borrensen-Dale, AL, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Kauppila, S, Andrulis, IL, Glendon, G, Mulligan, AM, Devilee, P, van Asperen, CJ, Tollenaar, RAEM, Seynaeve, C, Figueroa, JD, Garcia-Closas, M, Brinton, L, Lissowska, J, Hooning, M, Hollestelle, A, Oldenburg, R, van den Ouweland, A, Cox, A, Reed, MWR, Shah, M, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Jones, M, Schoemaker, M, Ashworth, A, Swerdlow, A, Beesley, J, Chen, XQ, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Chaiwerawattana, A, Kang, D, Yoo, KY, Noh, DY, Shen, CY, Yu, JC, Wu, PE, Hsiung, CN, Perkins, A, Swann, R, Velentzis, L, Eccles, DM, Tapper, WJ, Gerty, SM, Graham, NJ, Ponder, BAJ, Chenevix-Trench, G, Pharoah, PDP, Lathrop, M, Dunning, AM, Rahman, N, Peto, J & Easton, DF 2012, 'Genome-wide association analysis identifies three new breast cancer susceptibility loci', Nature Genetics, vol. 44, no. 3, pp. 312-U120. https://doi.org/10.1038/ng.1049

TY - JOUR

T1 - Genome-wide association analysis identifies three new breast cancer susceptibility loci

AU - Ghoussaini, M

AU - Fletcher, O

AU - Michailidou, K

AU - Turnbull, C

AU - Schmidt, Marjanka K

AU - Dicks, E

AU - Dennis, J

AU - Wang, Q (Qing)

AU - Humphreys, MK

AU - Luccarini, C

AU - Baynes, C

AU - Conroy, D

AU - Maranian, M

AU - Ahmed, S (Shahana)

AU - Driver, K

AU - Johnson, N

AU - Orr, N

AU - Silva, ID

AU - Waisfisz, Q

AU - Meijers-Heijboer, H

AU - Uitterlinden, André

AU - Rivadeneira, Fernando

AU - Hall, P

AU - Czene, K

AU - Irwanto, A

AU - Liu, JJ

AU - Nevanlinna, H

AU - Aittomaki, K

AU - Blomqvist, C

AU - Meindl, A

AU - Schmutzler, RK

AU - Muller-Myhsok, B

AU - Lichtner, P

AU - Chang-Claude, J

AU - Hein, R

AU - Nickels, S

AU - Flesch-Janys, D

AU - Tsimiklis, H

AU - Makalic, E

AU - Schmidt, D

AU - Bui, M

AU - Hopper, JL

AU - Apicella, C

AU - Park, DJ

AU - Southey, M

AU - Hunter, DJ

AU - Chanock, SJ

AU - Broeks, A

AU - Verhoef, S

AU - Hogervorst, FBL

AU - Fasching, PA

AU - Lux, MP

AU - Beckmann, MW

AU - Ekici, AB

AU - Sawyer, E

AU - Tomlinson, I

AU - Kerin, M

AU - Marme, F

AU - Schneeweiss, A

AU - Sohn, C

AU - Burwinkel, B

AU - Guenal, P

AU - Truong, T

AU - Cordina-Duverger, E

AU - Menegaux, F

AU - Bojesen, SE

AU - Nordestgaard, BG

AU - Nielsen, SF

AU - Flyger, H

AU - Milne, RL

AU - Alonso, MR

AU - Gonzalez-Neira, A

AU - Benitez, J

AU - Anton-Culver, H

AU - Ziogas, A

AU - Bernstein, L

AU - Dur, CC

AU - Brenner, H

AU - Muller, H

AU - Arndt, V

AU - Stegmaier, C

AU - Justenhoven, C

AU - Brauch, H

AU - Bruning, T

AU - Wang-Gohrke, S

AU - Eilber, U

AU - Dork, T

AU - Schurmann, P

AU - Bremer, M

AU - Hillemanns, P

AU - Bogdanova, NV

AU - Antonenkova, NN

AU - Rogov, YI

AU - Karstens, JH

AU - Bermisheva, M

AU - Prokofieva, D

AU - Khusnutdinova, E

AU - Lindblom, A

AU - Margolin, S

AU - Mannermaa, A

AU - Kataja, V

AU - Kosma, VM

AU - Hartikainen, JM

AU - Lambrechts, D

AU - Yesilyurt, BT

AU - Floris, G

AU - Leunen, K

AU - Manoukian, S

AU - Bonanni, B

AU - Fortuzzi, S

AU - Peterlongo, P

AU - Couch, FJ

AU - Wang, XS

AU - Stevens, K

AU - Lee, A

AU - Giles, GG

AU - Baglietto, L

AU - Severi, G

AU - McLean, C

AU - Alnaes, GG

AU - Kristensen, V

AU - Borrensen-Dale, AL

AU - John, EM

AU - Miron, A

AU - Winqvist, R

AU - Pylkas, K

AU - Jukkola-Vuorinen, A

AU - Kauppila, S

AU - Andrulis, IL

AU - Glendon, G

AU - Mulligan, AM

AU - Devilee, P

AU - van Asperen, CJ

AU - Tollenaar, RAEM

AU - Seynaeve, Caroline

AU - Figueroa, JD

AU - Garcia-Closas, M

AU - Brinton, L

AU - Lissowska, J

AU - Hooning, Maartje

AU - Hollestelle, Antoinette

AU - Oldenburg, Rogier

AU - van den Ouweland, Ans

AU - Cox, A

AU - Reed, MWR

AU - Shah, M

AU - Jakubowska, A

AU - Lubinski, J

AU - Jaworska, K

AU - Durda, K

AU - Jones, M

AU - Schoemaker, M

AU - Ashworth, A

AU - Swerdlow, A

AU - Beesley, J

AU - Chen, XQ

AU - Muir, KR

AU - Lophatananon, A

AU - Rattanamongkongul, S

AU - Chaiwerawattana, A

AU - Kang, D

AU - Yoo, KY

AU - Noh, DY

AU - Shen, CY

AU - Yu, JC

AU - Wu, PE

AU - Hsiung, CN

AU - Perkins, A

AU - Swann, R

AU - Velentzis, L

AU - Eccles, DM

AU - Tapper, WJ

AU - Gerty, SM

AU - Graham, NJ

AU - Ponder, BAJ

AU - Chenevix-Trench, G

AU - Pharoah, PDP

AU - Lathrop, M

AU - Dunning, AM

AU - Rahman, N

AU - Peto, J

AU - Easton, DF

PY - 2012

Y1 - 2012

N2 - Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for similar to 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in similar to 70,000 cases and similar to 68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 x 10(-35)), 12q24 (rs1292011; P = 4.3 x 10(-19)) and 21q21 (rs2823093; P = 1.1 x 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.

AB - Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for similar to 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in similar to 70,000 cases and similar to 68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 x 10(-35)), 12q24 (rs1292011; P = 4.3 x 10(-19)) and 21q21 (rs2823093; P = 1.1 x 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.

U2 - 10.1038/ng.1049

DO - 10.1038/ng.1049

M3 - Article

C2 - 22267197

SN - 1061-4036

VL - 44

SP - 312-U120

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -