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-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

External organisation

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

245 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

UN SDGs

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

SDG 3 Good Health and Well-being

Research programs

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

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.",

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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",

}

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 -