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

M Ghoussaini; O Fletcher; K Michailidou; C Turnbull; M K Schmidt; E Dicks; J Dennis; Q Wang; M K Humphreys; C Luccarini; C Baynes; D Conroy; M Maranian; S Ahmed; K Driver; N Johnson; N Orr; I dos Santos Silva; Q Waisfisz; H Meijers-Heijboer; A G Uitterlinden; F Rivadeneira; P Hall; K Czene; A Irwanto; J Liu; H Nevanlinna; K Aittomaki; C Blomqvist; A Meindl; R K Schmutzler; B Muller-Myhsok; P Lichtner; J Chang-Claude; R Hein; S Nickels; D Flesch-Janys; H Tsimiklis; E Makalic; D Schmidt; M Bui; J L Hopper; C Apicella; D J Park; M Southey; D J Hunter; S J Chanock; A Broeks; S Verhoef; F B Hogervorst; P A Fasching; M P Lux; M W Beckmann; A B Ekici; E Sawyer; I Tomlinson; M Kerin; F Marme; A Schneeweiss; C Sohn; B Burwinkel; P Guenel; T Truong; E Cordina-Duverger; F Menegaux; S E Bojesen; B G Nordestgaard; S F Nielsen; H Flyger; R L Milne; M R Alonso; A Gonzalez-Neira; J Benitez; H Anton-Culver; A Ziogas; L Bernstein; C C 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; N V Bogdanova; N N Antonenkova; Y I Rogov; J H Karstens; M Bermisheva; D Prokofieva; E Khusnutdinova; A Lindblom; S Margolin; A Mannermaa; V Kataja; V M Kosma; J M Hartikainen; D Lambrechts; B T Yesilyurt; G Floris; K Leunen; S Manoukian; B Bonanni; S Fortuzzi; P Peterlongo; F J Couch; X Wang; K Stevens; A Lee; G G Giles; L Baglietto; G Severi; C McLean; G G Alnaes; V Kristensen; A L Borrensen-Dale; E M John; A Miron; R Winqvist; K Pylkas; A Jukkola-Vuorinen; S Kauppila; I L Andrulis; G Glendon; A M Mulligan; P Devilee; C J van Asperen; R A Tollenaar; C Seynaeve; J D Figueroa; M Garcia-Closas; L Brinton; J Lissowska; M J Hooning; A Hollestelle; R A Oldenburg; A M van den Ouweland; A Cox; M W Reed; M Shah; A Jakubowska; J Lubinski; K Jaworska; K Durda; M Jones; M Schoemaker; A Ashworth; A Swerdlow; J Beesley; X Chen; K R Muir; A Lophatananon; S Rattanamongkongul; A Chaiwerawattana; D Kang; K Y Yoo; D Y Noh; C Y Shen; J C Yu; P E Wu; C N Hsiung; A Perkins; R Swann; L Velentzis; D M Eccles; W J Tapper; S M Gerty; N J Graham; B A Ponder; G Chenevix-Trench; P D Pharoah; M Lathrop; A M Dunning; N Rahman; J Peto; D F 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, M K Schmidt, E Dicks, J Dennis, Q Wang, M K Humphreys, C Luccarini, C Baynes, D Conroy, M Maranian, S Ahmed, K Driver, N Johnson, N Orr, I dos Santos Silva, Q Waisfisz, H Meijers-HeijboerA G Uitterlinden, F Rivadeneira, P Hall, K Czene, A Irwanto, J Liu, H Nevanlinna, K Aittomaki, C Blomqvist, A Meindl, R K Schmutzler, B Muller-Myhsok, P Lichtner, J Chang-Claude, R Hein, S Nickels, D Flesch-Janys, H Tsimiklis, E Makalic, D Schmidt, M Bui, J L Hopper, C Apicella, D J Park, M Southey, D J Hunter, S J Chanock, A Broeks, S Verhoef, F B Hogervorst, P A Fasching, M P Lux, M W Beckmann, A B Ekici, E Sawyer, I Tomlinson, M Kerin, F Marme, A Schneeweiss, C Sohn, B Burwinkel, P Guenel, T Truong, E Cordina-Duverger, F Menegaux, S E Bojesen, B G Nordestgaard, S F Nielsen, H Flyger, R L Milne, M R Alonso, A Gonzalez-Neira, J Benitez, H Anton-Culver, A Ziogas, L Bernstein, C C 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, N V Bogdanova, N N Antonenkova, Y I Rogov, J H Karstens, M Bermisheva, D Prokofieva, E Khusnutdinova, A Lindblom, S Margolin, A Mannermaa, V Kataja, V M Kosma, J M Hartikainen, D Lambrechts, B T Yesilyurt, G Floris, K Leunen, S Manoukian, B Bonanni, S Fortuzzi, P Peterlongo, F J Couch, X Wang, K Stevens, A Lee, G G Giles, L Baglietto, G Severi, C McLean, G G Alnaes, V Kristensen, A L Borrensen-Dale, E M John, A Miron, R Winqvist, K Pylkas, A Jukkola-Vuorinen, S Kauppila, I L Andrulis, G Glendon, A M Mulligan, P Devilee, C J van Asperen, R A Tollenaar, C Seynaeve, J D Figueroa, M Garcia-Closas, L Brinton, J Lissowska, M J Hooning, A Hollestelle, R A Oldenburg, A M van den Ouweland, A Cox, M W Reed, M Shah, A Jakubowska, J Lubinski, K Jaworska, K Durda, M Jones, M Schoemaker, A Ashworth, A Swerdlow, J Beesley, X Chen, K R Muir, A Lophatananon, S Rattanamongkongul, A Chaiwerawattana, D Kang, K Y Yoo, D Y Noh, C Y Shen, J C Yu, P E Wu, C N Hsiung, A Perkins, R Swann, L Velentzis, D M Eccles, W J Tapper, S M Gerty, N J Graham, B A Ponder, G Chenevix-Trench, P D Pharoah, M Lathrop, A M Dunning, N Rahman, J Peto, D F Easton

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

Abstract

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for approximately 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in approximately 70,000 cases and approximately 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	English
Pages (from-to)	312-8
Number of pages	303
Journal	Nat Genet
Volume	44
Issue number	3
DOIs	https://doi.org/10.1038/ng.1049
Publication status	Published - 2012

Keywords

Breast Neoplasms/ genetics
Chromosomes, Human, Pair 12/ genetics
Chromosomes, Human, Pair 21/ genetics
European Continental Ancestry Group/genetics
Female
Genetic Loci/ genetics
Genetic Predisposition to Disease/ genetics
Genome-Wide Association Study
Humans
Logistic Models
Polymorphism, Single Nucleotide/genetics
Principal Component Analysis

UN SDGs

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

Access to Document

10.1038/ng.1049

Cite this

Ghoussaini, M., Fletcher, O., Michailidou, K., Turnbull, C., Schmidt, M. K., Dicks, E., Dennis, J., Wang, Q., Humphreys, M. K., Luccarini, C., Baynes, C., Conroy, D., Maranian, M., Ahmed, S., Driver, K., Johnson, N., Orr, N., dos Santos Silva, I., Waisfisz, Q., ... Easton, D. F. (2012). Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nat Genet, 44(3), 312-8. https://doi.org/10.1038/ng.1049

@article{629e58a2a9ba4a60963cd62e65a78c30,

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 approximately 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in approximately 70,000 cases and approximately 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.",

keywords = "Breast Neoplasms/ genetics, Chromosomes, Human, Pair 12/ genetics, Chromosomes, Human, Pair 21/ genetics, European Continental Ancestry Group/genetics, Female, Genetic Loci/ genetics, Genetic Predisposition to Disease/ genetics, Genome-Wide Association Study, Humans, Logistic Models, Polymorphism, Single Nucleotide/genetics, Principal Component Analysis",

author = "M Ghoussaini and O Fletcher and K Michailidou and C Turnbull and Schmidt, {M K} and E Dicks and J Dennis and Q Wang and Humphreys, {M K} and C Luccarini and C Baynes and D Conroy and M Maranian and S Ahmed and K Driver and N Johnson and N Orr and {dos Santos Silva}, I and Q Waisfisz and H Meijers-Heijboer and Uitterlinden, {A G} and F Rivadeneira and P Hall and K Czene and A Irwanto and J Liu and H Nevanlinna and K Aittomaki and C Blomqvist and A Meindl and Schmutzler, {R K} 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 Hopper, {J L} and C Apicella and Park, {D J} and M Southey and Hunter, {D J} and Chanock, {S J} and A Broeks and S Verhoef and Hogervorst, {F B} and Fasching, {P A} and Lux, {M P} and Beckmann, {M W} and Ekici, {A B} and E Sawyer and I Tomlinson and M Kerin and F Marme and A Schneeweiss and C Sohn and B Burwinkel and P Guenel and T Truong and E Cordina-Duverger and F Menegaux and Bojesen, {S E} and Nordestgaard, {B G} and Nielsen, {S F} and H Flyger and Milne, {R L} and Alonso, {M R} and A Gonzalez-Neira and J Benitez and H Anton-Culver and A Ziogas and L Bernstein and Dur, {C C} 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 Bogdanova, {N V} and Antonenkova, {N N} and Rogov, {Y I} and Karstens, {J H} and M Bermisheva and D Prokofieva and E Khusnutdinova and A Lindblom and S Margolin and A Mannermaa and V Kataja and Kosma, {V M} and Hartikainen, {J M} and D Lambrechts and Yesilyurt, {B T} and G Floris and K Leunen and S Manoukian and B Bonanni and S Fortuzzi and P Peterlongo and Couch, {F J} and X Wang and K Stevens and A Lee and Giles, {G G} and L Baglietto and G Severi and C McLean and Alnaes, {G G} and V Kristensen and Borrensen-Dale, {A L} and John, {E M} and A Miron and R Winqvist and K Pylkas and A Jukkola-Vuorinen and S Kauppila and Andrulis, {I L} and G Glendon and Mulligan, {A M} and P Devilee and {van Asperen}, {C J} and Tollenaar, {R A} and C Seynaeve and Figueroa, {J D} and M Garcia-Closas and L Brinton and J Lissowska and Hooning, {M J} and A Hollestelle and Oldenburg, {R A} and {van den Ouweland}, {A M} and A Cox and Reed, {M W} 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 X Chen and Muir, {K R} and A Lophatananon and S Rattanamongkongul and A Chaiwerawattana and D Kang and Yoo, {K Y} and Noh, {D Y} and Shen, {C Y} and Yu, {J C} and Wu, {P E} and Hsiung, {C N} and A Perkins and R Swann and L Velentzis and Eccles, {D M} and Tapper, {W J} and Gerty, {S M} and Graham, {N J} and Ponder, {B A} and G Chenevix-Trench and Pharoah, {P D} and M Lathrop and Dunning, {A M} and N Rahman and J Peto and Easton, {D F}",

note = "Ghoussaini, Maya Fletcher, Olivia Michailidou, Kyriaki Turnbull, Clare Schmidt, Marjanka K Dicks, Ed Dennis, Joe Wang, Qin Humphreys, Manjeet K Luccarini, Craig Baynes, Caroline Conroy, Don Maranian, Melanie Ahmed, Shahana Driver, Kristy Johnson, Nichola Orr, Nicholas dos Santos Silva, Isabel Waisfisz, Quinten Meijers-Heijboer, Hanne Uitterlinden, Andre G Rivadeneira, Fernando Netherlands Collaborative Group on Hereditary Breast and Ovarian Cancer (HEBON) Hall, Per Czene, Kamila Irwanto, Astrid Liu, Jianjun Nevanlinna, Heli Aittomaki, Kristiina Blomqvist, Carl Meindl, Alfons Schmutzler, Rita K Muller-Myhsok, Bertram Lichtner, Peter Chang-Claude, Jenny Hein, Rebecca Nickels, Stefan Flesch-Janys, Dieter Tsimiklis, Helen Makalic, Enes Schmidt, Daniel Bui, Minh Hopper, John L Apicella, Carmel Park, Daniel J Southey, Melissa Hunter, David J Chanock, Stephen J Broeks, Annegien Verhoef, Senno Hogervorst, Frans B L Fasching, Peter A Lux, Michael P Beckmann, Matthias W Ekici, Arif B Sawyer, Elinor Tomlinson, Ian Kerin, Michael Marme, Frederik Schneeweiss, Andreas Sohn, Christof Burwinkel, Barbara Guenel, Pascal Truong, Therese Cordina-Duverger, Emilie Menegaux, Florence Bojesen, Stig E Nordestgaard, Borge G Nielsen, Sune F Flyger, Henrik Milne, Roger L Alonso, M Rosario Gonzalez-Neira, Anna Benitez, Javier Anton-Culver, Hoda Ziogas, Argyrios Bernstein, Leslie Dur, Christina Clarke Brenner, Hermann Muller, Heiko Arndt, Volker Stegmaier, Christa Familial Breast Cancer Study (FBCS) Justenhoven, Christina Brauch, Hiltrud Bruning, Thomas Gene Environment Interaction of Breast Cancer in Germany (GENICA) Network Wang-Gohrke, Shan Eilber, Ursula Dork, Thilo Schurmann, Peter Bremer, Michael Hillemanns, Peter Bogdanova, Natalia V Antonenkova, Natalia N Rogov, Yuri I Karstens, Johann H Bermisheva, Marina Prokofieva, Darya Khusnutdinova, Elza Lindblom, Annika Margolin, Sara Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M Lambrechts, Diether Yesilyurt, Betul T Floris, Giuseppe Leunen, Karin Manoukian, Siranoush Bonanni, Bernardo Fortuzzi, Stefano Peterlongo, Paolo Couch, Fergus J Wang, Xianshu Stevens, Kristen Lee, Adam Giles, Graham G Baglietto, Laura Severi, Gianluca McLean, Catriona Alnaes, Grethe Grenaker Kristensen, Vessela Borrensen-Dale, Anne-Lise John, Esther M Miron, Alexander Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Kauppila, Saila Andrulis, Irene L Glendon, Gord Mulligan, Anna Marie Devilee, Peter van Asperen, Christie J Tollenaar, Rob A E M Seynaeve, Caroline Figueroa, Jonine D Garcia-Closas, Montserrat Brinton, Louise Lissowska, Jolanta Hooning, Maartje J Hollestelle, Antoinette Oldenburg, Rogier A van den Ouweland, Ans M W Cox, Angela Reed, Malcolm W R Shah, Mitul Jakubowska, Ania Lubinski, Jan Jaworska, Katarzyna Durda, Katarzyna Jones, Michael Schoemaker, Minouk Ashworth, Alan Swerdlow, Anthony Beesley, Jonathan Chen, Xiaoqing kConFab Investigators Australian Ovarian Cancer Study Group Muir, Kenneth R Lophatananon, Artitaya Rattanamongkongul, Suthee Chaiwerawattana, Arkom Kang, Daehee Yoo, Keun-Young Noh, Dong-Young Shen, Chen-Yang Yu, Jyh-Cherng Wu, Pei-Ei Hsiung, Chia-Ni Perkins, Annie Swann, Ruth Velentzis, Louiza Eccles, Diana M Tapper, Will J Gerty, Susan M Graham, Nikki J Ponder, Bruce A J Chenevix-Trench, Georgia Pharoah, Paul D P Lathrop, Mark Dunning, Alison M Rahman, Nazneen Peto, Julian Easton, Douglas F Meta-Analysis United States Nature genetics Nat Genet. 2012 Jan 22;44(3):312-8. doi: 10.1038/ng.1049.",

year = "2012",

doi = "10.1038/ng.1049",

language = "English",

volume = "44",

pages = "312--8",

journal = "Nat Genet",

issn = "1546-1718",

publisher = "Springer Nature",

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, dos Santos Silva, I, Waisfisz, Q, Meijers-Heijboer, H, Uitterlinden, AG, Rivadeneira, F, Hall, P, Czene, K, Irwanto, A, Liu, J, 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, FB, Fasching, PA, Lux, MP, Beckmann, MW, Ekici, AB, Sawyer, E, Tomlinson, I, Kerin, M, Marme, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guenel, 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, X, 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, RA, Seynaeve, C, Figueroa, JD, Garcia-Closas, M, Brinton, L, Lissowska, J, Hooning, MJ, Hollestelle, A, Oldenburg, RA, van den Ouweland, AM, Cox, A, Reed, MW, Shah, M, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Jones, M, Schoemaker, M, Ashworth, A, Swerdlow, A, Beesley, J, Chen, X, 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, BA, Chenevix-Trench, G, Pharoah, PD, Lathrop, M, Dunning, AM, Rahman, N, Peto, J & Easton, DF 2012, 'Genome-wide association analysis identifies three new breast cancer susceptibility loci', Nat Genet, vol. 44, no. 3, pp. 312-8. 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, M K

AU - Dicks, E

AU - Dennis, J

AU - Wang, Q

AU - Humphreys, M K

AU - Luccarini, C

AU - Baynes, C

AU - Conroy, D

AU - Maranian, M

AU - Ahmed, S

AU - Driver, K

AU - Johnson, N

AU - Orr, N

AU - dos Santos Silva, I

AU - Waisfisz, Q

AU - Meijers-Heijboer, H

AU - Uitterlinden, A G

AU - Rivadeneira, F

AU - Hall, P

AU - Czene, K

AU - Irwanto, A

AU - Liu, J

AU - Nevanlinna, H

AU - Aittomaki, K

AU - Blomqvist, C

AU - Meindl, A

AU - Schmutzler, R K

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, J L

AU - Apicella, C

AU - Park, D J

AU - Southey, M

AU - Hunter, D J

AU - Chanock, S J

AU - Broeks, A

AU - Verhoef, S

AU - Hogervorst, F B

AU - Fasching, P A

AU - Lux, M P

AU - Beckmann, M W

AU - Ekici, A B

AU - Sawyer, E

AU - Tomlinson, I

AU - Kerin, M

AU - Marme, F

AU - Schneeweiss, A

AU - Sohn, C

AU - Burwinkel, B

AU - Guenel, P

AU - Truong, T

AU - Cordina-Duverger, E

AU - Menegaux, F

AU - Bojesen, S E

AU - Nordestgaard, B G

AU - Nielsen, S F

AU - Flyger, H

AU - Milne, R L

AU - Alonso, M R

AU - Gonzalez-Neira, A

AU - Benitez, J

AU - Anton-Culver, H

AU - Ziogas, A

AU - Bernstein, L

AU - Dur, C C

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, N V

AU - Antonenkova, N N

AU - Rogov, Y I

AU - Karstens, J H

AU - Bermisheva, M

AU - Prokofieva, D

AU - Khusnutdinova, E

AU - Lindblom, A

AU - Margolin, S

AU - Mannermaa, A

AU - Kataja, V

AU - Kosma, V M

AU - Hartikainen, J M

AU - Lambrechts, D

AU - Yesilyurt, B T

AU - Floris, G

AU - Leunen, K

AU - Manoukian, S

AU - Bonanni, B

AU - Fortuzzi, S

AU - Peterlongo, P

AU - Couch, F J

AU - Wang, X

AU - Stevens, K

AU - Lee, A

AU - Giles, G G

AU - Baglietto, L

AU - Severi, G

AU - McLean, C

AU - Alnaes, G G

AU - Kristensen, V

AU - Borrensen-Dale, A L

AU - John, E M

AU - Miron, A

AU - Winqvist, R

AU - Pylkas, K

AU - Jukkola-Vuorinen, A

AU - Kauppila, S

AU - Andrulis, I L

AU - Glendon, G

AU - Mulligan, A M

AU - Devilee, P

AU - van Asperen, C J

AU - Tollenaar, R A

AU - Seynaeve, C

AU - Figueroa, J D

AU - Garcia-Closas, M

AU - Brinton, L

AU - Lissowska, J

AU - Hooning, M J

AU - Hollestelle, A

AU - Oldenburg, R A

AU - van den Ouweland, A M

AU - Cox, A

AU - Reed, M W

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, X

AU - Muir, K R

AU - Lophatananon, A

AU - Rattanamongkongul, S

AU - Chaiwerawattana, A

AU - Kang, D

AU - Yoo, K Y

AU - Noh, D Y

AU - Shen, C Y

AU - Yu, J C

AU - Wu, P E

AU - Hsiung, C N

AU - Perkins, A

AU - Swann, R

AU - Velentzis, L

AU - Eccles, D M

AU - Tapper, W J

AU - Gerty, S M

AU - Graham, N J

AU - Ponder, B A

AU - Chenevix-Trench, G

AU - Pharoah, P D

AU - Lathrop, M

AU - Dunning, A M

AU - Rahman, N

AU - Peto, J

AU - Easton, D F

N1 - Ghoussaini, Maya Fletcher, Olivia Michailidou, Kyriaki Turnbull, Clare Schmidt, Marjanka K Dicks, Ed Dennis, Joe Wang, Qin Humphreys, Manjeet K Luccarini, Craig Baynes, Caroline Conroy, Don Maranian, Melanie Ahmed, Shahana Driver, Kristy Johnson, Nichola Orr, Nicholas dos Santos Silva, Isabel Waisfisz, Quinten Meijers-Heijboer, Hanne Uitterlinden, Andre G Rivadeneira, Fernando Netherlands Collaborative Group on Hereditary Breast and Ovarian Cancer (HEBON) Hall, Per Czene, Kamila Irwanto, Astrid Liu, Jianjun Nevanlinna, Heli Aittomaki, Kristiina Blomqvist, Carl Meindl, Alfons Schmutzler, Rita K Muller-Myhsok, Bertram Lichtner, Peter Chang-Claude, Jenny Hein, Rebecca Nickels, Stefan Flesch-Janys, Dieter Tsimiklis, Helen Makalic, Enes Schmidt, Daniel Bui, Minh Hopper, John L Apicella, Carmel Park, Daniel J Southey, Melissa Hunter, David J Chanock, Stephen J Broeks, Annegien Verhoef, Senno Hogervorst, Frans B L Fasching, Peter A Lux, Michael P Beckmann, Matthias W Ekici, Arif B Sawyer, Elinor Tomlinson, Ian Kerin, Michael Marme, Frederik Schneeweiss, Andreas Sohn, Christof Burwinkel, Barbara Guenel, Pascal Truong, Therese Cordina-Duverger, Emilie Menegaux, Florence Bojesen, Stig E Nordestgaard, Borge G Nielsen, Sune F Flyger, Henrik Milne, Roger L Alonso, M Rosario Gonzalez-Neira, Anna Benitez, Javier Anton-Culver, Hoda Ziogas, Argyrios Bernstein, Leslie Dur, Christina Clarke Brenner, Hermann Muller, Heiko Arndt, Volker Stegmaier, Christa Familial Breast Cancer Study (FBCS) Justenhoven, Christina Brauch, Hiltrud Bruning, Thomas Gene Environment Interaction of Breast Cancer in Germany (GENICA) Network Wang-Gohrke, Shan Eilber, Ursula Dork, Thilo Schurmann, Peter Bremer, Michael Hillemanns, Peter Bogdanova, Natalia V Antonenkova, Natalia N Rogov, Yuri I Karstens, Johann H Bermisheva, Marina Prokofieva, Darya Khusnutdinova, Elza Lindblom, Annika Margolin, Sara Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M Lambrechts, Diether Yesilyurt, Betul T Floris, Giuseppe Leunen, Karin Manoukian, Siranoush Bonanni, Bernardo Fortuzzi, Stefano Peterlongo, Paolo Couch, Fergus J Wang, Xianshu Stevens, Kristen Lee, Adam Giles, Graham G Baglietto, Laura Severi, Gianluca McLean, Catriona Alnaes, Grethe Grenaker Kristensen, Vessela Borrensen-Dale, Anne-Lise John, Esther M Miron, Alexander Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Kauppila, Saila Andrulis, Irene L Glendon, Gord Mulligan, Anna Marie Devilee, Peter van Asperen, Christie J Tollenaar, Rob A E M Seynaeve, Caroline Figueroa, Jonine D Garcia-Closas, Montserrat Brinton, Louise Lissowska, Jolanta Hooning, Maartje J Hollestelle, Antoinette Oldenburg, Rogier A van den Ouweland, Ans M W Cox, Angela Reed, Malcolm W R Shah, Mitul Jakubowska, Ania Lubinski, Jan Jaworska, Katarzyna Durda, Katarzyna Jones, Michael Schoemaker, Minouk Ashworth, Alan Swerdlow, Anthony Beesley, Jonathan Chen, Xiaoqing kConFab Investigators Australian Ovarian Cancer Study Group Muir, Kenneth R Lophatananon, Artitaya Rattanamongkongul, Suthee Chaiwerawattana, Arkom Kang, Daehee Yoo, Keun-Young Noh, Dong-Young Shen, Chen-Yang Yu, Jyh-Cherng Wu, Pei-Ei Hsiung, Chia-Ni Perkins, Annie Swann, Ruth Velentzis, Louiza Eccles, Diana M Tapper, Will J Gerty, Susan M Graham, Nikki J Ponder, Bruce A J Chenevix-Trench, Georgia Pharoah, Paul D P Lathrop, Mark Dunning, Alison M Rahman, Nazneen Peto, Julian Easton, Douglas F Meta-Analysis United States Nature genetics Nat Genet. 2012 Jan 22;44(3):312-8. doi: 10.1038/ng.1049.

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 approximately 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in approximately 70,000 cases and approximately 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 approximately 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in approximately 70,000 cases and approximately 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.

KW - Breast Neoplasms/ genetics

KW - Chromosomes, Human, Pair 12/ genetics

KW - Chromosomes, Human, Pair 21/ genetics

KW - European Continental Ancestry Group/genetics

KW - Female

KW - Genetic Loci/ genetics

KW - Genetic Predisposition to Disease/ genetics

KW - Genome-Wide Association Study

KW - Humans

KW - Logistic Models

KW - Polymorphism, Single Nucleotide/genetics

KW - Principal Component Analysis

U2 - 10.1038/ng.1049

DO - 10.1038/ng.1049

M3 - Article

SN - 1546-1718

VL - 44

SP - 312

EP - 318

JO - Nat Genet

JF - Nat Genet

IS - 3

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this