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 C Southey; David J Hunter; Stephen J.  Chanock; Annegien Broeks; Senno Verhoef; Frans B L Hogervorst; 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-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 C Southey, David J Hunter, Stephen J. Chanock, Annegien Broeks, Senno Verhoef, Frans B L Hogervorst, Netherlands Collaborative Group on Hereditary Breast and Ovarian Cancer (HEBON)

School of Medicine, Dentistry and Biomedical Sciences

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

249 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 ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ∼70,000 cases and ∼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 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 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	7
Journal	Nature Genetics
Volume	44
Issue number	3
DOIs	https://doi.org/10.1038/ng.1049
Publication status	Published - 22 Jan 2012

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

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

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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., ... 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

@article{dd35024f01d44ccf8653bc71bc8dfff2,

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 ∼8\% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ∼70,000 cases and ∼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 {\texttimes} 10(-35)), 12q24 (rs1292011; P = 4.3 {\texttimes} 10(-19)) and 21q21 (rs2823093; P = 1.1 {\texttimes} 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, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 21, European Continental Ancestry Group, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Logistic Models, Polymorphism, Single Nucleotide, Principal Component Analysis, Journal Article, Meta-Analysis",

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 Isabel Dos-Santos-Silva 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 Southey, \{Melissa C\} and Hunter, \{David J\} and Chanock, \{Stephen J.\} and Annegien Broeks and Senno Verhoef and Hogervorst, \{Frans B L\} and \{Netherlands Collaborative Group on Hereditary Breast and Ovarian Cancer (HEBON)\}",

year = "2012",

month = jan,

day = "22",

doi = "10.1038/ng.1049",

language = "English",

volume = "44",

pages = "312--8",

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, 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, MC, Hunter, DJ, Chanock, SJ, Broeks, A, Verhoef, S, Hogervorst, FBL & 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

TY - JOUR

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 C

AU - Hunter, David J

AU - Chanock, Stephen J.

AU - Broeks, Annegien

AU - Verhoef, Senno

AU - Hogervorst, Frans B L

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

PY - 2012/1/22

Y1 - 2012/1/22

N2 - Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ∼70,000 cases and ∼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 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 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 ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ∼70,000 cases and ∼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 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 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

KW - Chromosomes, Human, Pair 12

KW - Chromosomes, Human, Pair 21

KW - European Continental Ancestry Group

KW - Female

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Logistic Models

KW - Polymorphism, Single Nucleotide

KW - Principal Component Analysis

KW - Journal Article

KW - Meta-Analysis

U2 - 10.1038/ng.1049

DO - 10.1038/ng.1049

M3 - Article

C2 - 22267197

SN - 1061-4036

VL - 44

SP - 312

EP - 318

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

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

Abstract

UN SDGs

Keywords

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