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

Maya Ghoussaini; Olivia Fletcher; Kyriaki Michailidou; Clare Turnbull; Marjanka K Schmidt; Ed Dicks; Joe Dennis; Qin Wang; Manjeet K Humphreys; Craig Luccarini; Caroline Baynes; Don Conroy; Melanie Maranian; Shahana Ahmed; Kristy Driver; Nichola Johnson; Nicholas Orr; Isabel dos Santos Silva; Quinten Waisfisz; Hanne Meijers-Heijboer; Andre G Uitterlinden; Fernando Rivadeneira; Per Hall; Kamila Czene; Astrid Irwanto; Jianjun Liu; Heli Nevanlinna; Kristiina Aittomäki; Carl Blomqvist; Alfons Meindl; Rita K Schmutzler; Bertram Müller-Myhsok; Peter Lichtner; Jenny Chang-Claude; Rebecca Hein; Stefan Nickels; Dieter Flesch-Janys; Helen Tsimiklis; Enes Makalic; Daniel Schmidt; Minh Bui; John L Hopper; Carmel Apicella; Daniel J Park; Melissa Southey; David J Hunter; Stephen J Chanock; Annegien Broeks; Senno Verhoef; Børge G Nordestgaard; Netherlands Collaborative Group on Hereditary Breast and Ovarian Cancer (HEBON)

doi:10.1038/ng.1049

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

Maya Ghoussaini, Olivia Fletcher, Kyriaki Michailidou, Clare Turnbull, Marjanka K Schmidt, Ed Dicks, Joe Dennis, Qin Wang, Manjeet K Humphreys, Craig Luccarini, Caroline Baynes, Don Conroy, Melanie Maranian, Shahana Ahmed, Kristy Driver, Nichola Johnson, Nicholas Orr, Isabel dos Santos Silva, Quinten Waisfisz, Hanne Meijers-HeijboerAndre G Uitterlinden, Fernando Rivadeneira, Per Hall, Kamila Czene, Astrid Irwanto, Jianjun Liu, Heli Nevanlinna, Kristiina Aittomäki, Carl Blomqvist, Alfons Meindl, Rita K Schmutzler, Bertram Müller-Myhsok, Peter Lichtner, Jenny Chang-Claude, Rebecca Hein, Stefan Nickels, Dieter Flesch-Janys, Helen Tsimiklis, Enes Makalic, Daniel Schmidt, Minh Bui, John L Hopper, Carmel Apicella, Daniel J Park, Melissa Southey, David J Hunter, Stephen J Chanock, Annegien Broeks, Senno Verhoef, Børge G Nordestgaard, Netherlands Collaborative Group on Hereditary Breast and Ovarian Cancer (HEBON)

218 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 g1/48% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in g1/470,000 cases and ĝ̂1/468,000 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 - 10 g³⁵), 12q24 (rs1292011; P = 4.3 - 10 g¹⁹) and 21q21 (rs2823093; P = 1.1 - 10 g¹²). 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
Journal	Nature Genetics
Volume	44
Issue number	3
Pages (from-to)	312-8
Number of pages	7
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.1049
Publication status	Published - Mar 2012

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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., ... Netherlands Collaborative Group on Hereditary Breast and Ovarian Cancer (HEBON) (2012). Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nature Genetics, 44(3), 312-8. https://doi.org/10.1038/ng.1049

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, Aittomäki, K, Blomqvist, C, Meindl, A, Schmutzler, RK, Müller-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, Nordestgaard, BG & Netherlands Collaborative Group on Hereditary Breast and Ovarian Cancer (HEBON) 2012, 'Genome-wide association analysis identifies three new breast cancer susceptibility loci', Nature Genetics, vol. 44, no. 3, pp. 312-8. https://doi.org/10.1038/ng.1049

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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 g1/48% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in g1/470,000 cases and {\^ĝ}1/468,000 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 - 10 g35), 12q24 (rs1292011; P = 4.3 - 10 g19) and 21q21 (rs2823093; P = 1.1 - 10 g12). 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 = "Maya Ghoussaini and Olivia Fletcher and Kyriaki Michailidou and Clare Turnbull and Schmidt, {Marjanka K} and Ed Dicks and Joe Dennis and Qin Wang and Humphreys, {Manjeet K} and Craig Luccarini and Caroline Baynes and Don Conroy and Melanie Maranian and Shahana Ahmed and Kristy Driver and Nichola Johnson and Nicholas Orr and {dos Santos Silva}, Isabel and Quinten Waisfisz and Hanne Meijers-Heijboer and Uitterlinden, {Andre G} and Fernando Rivadeneira and Per Hall and Kamila Czene and Astrid Irwanto and Jianjun Liu and Heli Nevanlinna and Kristiina Aittom{\"a}ki and Carl Blomqvist and Alfons Meindl and Schmutzler, {Rita K} and Bertram M{\"u}ller-Myhsok and Peter Lichtner and Jenny Chang-Claude and Rebecca Hein and Stefan Nickels and Dieter Flesch-Janys and Helen Tsimiklis and Enes Makalic and Daniel Schmidt and Minh Bui and Hopper, {John L} and Carmel Apicella and Park, {Daniel J} and Melissa Southey and Hunter, {David J} and Chanock, {Stephen J} and Annegien Broeks and Senno Verhoef and Nordestgaard, {B{\o}rge G} and B{\o}rge Nordestgaard",

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doi = "10.1038/ng.1049",

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

AU - Ghoussaini, Maya

AU - Fletcher, Olivia

AU - Michailidou, Kyriaki

AU - Turnbull, Clare

AU - Schmidt, Marjanka K

AU - Dicks, Ed

AU - Dennis, Joe

AU - Wang, Qin

AU - Humphreys, Manjeet K

AU - Luccarini, Craig

AU - Baynes, Caroline

AU - Conroy, Don

AU - Maranian, Melanie

AU - Ahmed, Shahana

AU - Driver, Kristy

AU - Johnson, Nichola

AU - Orr, Nicholas

AU - dos Santos Silva, Isabel

AU - Waisfisz, Quinten

AU - Meijers-Heijboer, Hanne

AU - Uitterlinden, Andre G

AU - Rivadeneira, Fernando

AU - Hall, Per

AU - Czene, Kamila

AU - Irwanto, Astrid

AU - Liu, Jianjun

AU - Nevanlinna, Heli

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Meindl, Alfons

AU - Schmutzler, Rita K

AU - Müller-Myhsok, Bertram

AU - Lichtner, Peter

AU - Chang-Claude, Jenny

AU - Hein, Rebecca

AU - Nickels, Stefan

AU - Flesch-Janys, Dieter

AU - Tsimiklis, Helen

AU - Makalic, Enes

AU - Schmidt, Daniel

AU - Bui, Minh

AU - Hopper, John L

AU - Apicella, Carmel

AU - Park, Daniel J

AU - Southey, Melissa

AU - Hunter, David J

AU - Chanock, Stephen J

AU - Broeks, Annegien

AU - Verhoef, Senno

AU - Nordestgaard, Børge G

AU - Netherlands Collaborative Group on Hereditary Breast and Ovarian Cancer (HEBON)

PY - 2012/3

Y1 - 2012/3

N2 - Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for g1/48% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in g1/470,000 cases and ĝ̂1/468,000 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 - 10 g35), 12q24 (rs1292011; P = 4.3 - 10 g19) and 21q21 (rs2823093; P = 1.1 - 10 g12). 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 g1/48% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in g1/470,000 cases and ĝ̂1/468,000 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 - 10 g35), 12q24 (rs1292011; P = 4.3 - 10 g19) and 21q21 (rs2823093; P = 1.1 - 10 g12). 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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DO - 10.1038/ng.1049

M3 - Journal article

C2 - 22267197

SN - 1061-4036

VL - 44

SP - 312

EP - 318

JO - Nature: New biology

JF - Nature: New biology

IS - 3

ER -

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

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