Genome-wide association studies identify four ER negative-specific breast cancer risk loci

Montserrat Garcia-Closas; Fergus J Couch; Sara Lindstrom; Kyriaki Michailidou; Marjanka K. Schmidt; Mark N. Brook; Nick Orr; Suhn Kyong Rhie; Elio B Riboli; Heather Spencer Feigelson; Loic Le Marchand; Julie E Buring; Diana M Eccles; Penelope Miron; Peter A. Fasching; Hiltrud Brauch; Jenny Chang-Claude; Jane Carpenter; Andrew K. Godwin; Heli Nevanlinna; Graham G. Giles; Melissa C. Southey; Catriona McLean; Enes Makalic

doi:10.1038/ng.2561

Genome-wide association studies identify four ER negative-specific breast cancer risk loci

Montserrat Garcia-Closas
, Fergus J Couch
, Sara Lindstrom
, Kyriaki Michailidou
, Marjanka K. Schmidt
, Mark N. Brook
, Nick Orr
, Suhn Kyong Rhie
, Elio B Riboli
, Heather Spencer Feigelson
, Loic Le Marchand
, Julie E Buring
, Diana M Eccles
, Penelope Miron
, Peter A. Fasching
, Hiltrud Brauch
, Jenny Chang-Claude
, Jane Carpenter
, Andrew K. Godwin
, Heli Nevanlinna

Graham G. Giles, Melissa C. Southey, Catriona McLean, Enes Makalic

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

353 Citations (Scopus)

Abstract

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10^-12 and LGR6, P = 1.4 × 10^-8), 2p24.1 (P = 4.6 × 10^-8) and 16q12.2 (FTO, P = 4.0 × 10^-8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

Original language	English
Pages (from-to)	392-398
Number of pages	7
Journal	Nature Genetics
Volume	45
Issue number	4
DOIs	https://doi.org/10.1038/ng.2561
Publication status	Published - Apr 2013
Externally published	Yes

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SDG 3 Good Health and Well-being

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127399145-oaAccepted author manuscript, 353 KB

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Garcia-Closas, M., Couch, F. J., Lindstrom, S., Michailidou, K., Schmidt, M. K., Brook, M. N., Orr, N., Rhie, S. K., Riboli, E. B., Feigelson, H. S., Le Marchand, L., Buring, J. E., Eccles, D. M., Miron, P., Fasching, P. A., Brauch, H., Chang-Claude, J., Carpenter, J., Godwin, A. K., ... Makalic, E. (2013). Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nature Genetics, 45(4), 392-398. https://doi.org/10.1038/ng.2561

@article{7325b77c86d745939ed190a6fd920047,

title = "Genome-wide association studies identify four ER negative-specific breast cancer risk loci",

abstract = "Estrogen receptor (ER)-negative tumors represent 20-30\% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10-12 and LGR6, P = 1.4 × 10-8), 2p24.1 (P = 4.6 × 10-8) and 16q12.2 (FTO, P = 4.0 × 10-8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.",

author = "Montserrat Garcia-Closas and Couch, \{Fergus J\} and Sara Lindstrom and Kyriaki Michailidou and Schmidt, \{Marjanka K.\} and Brook, \{Mark N.\} and Nick Orr and Rhie, \{Suhn Kyong\} and Riboli, \{Elio B\} and Feigelson, \{Heather Spencer\} and \{Le Marchand\}, Loic and Buring, \{Julie E\} and Eccles, \{Diana M\} and Penelope Miron and Fasching, \{Peter A.\} and Hiltrud Brauch and Jenny Chang-Claude and Jane Carpenter and Godwin, \{Andrew K.\} and Heli Nevanlinna and Giles, \{Graham G.\} and Southey, \{Melissa C.\} and Catriona McLean and Enes Makalic",

year = "2013",

month = apr,

doi = "10.1038/ng.2561",

language = "English",

volume = "45",

pages = "392--398",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "4",

}

Garcia-Closas, M, Couch, FJ, Lindstrom, S, Michailidou, K, Schmidt, MK, Brook, MN, Orr, N, Rhie, SK, Riboli, EB, Feigelson, HS, Le Marchand, L, Buring, JE, Eccles, DM, Miron, P, Fasching, PA, Brauch, H, Chang-Claude, J, Carpenter, J, Godwin, AK, Nevanlinna, H, Giles, GG, Southey, MC , McLean, C & Makalic, E 2013, 'Genome-wide association studies identify four ER negative-specific breast cancer risk loci', Nature Genetics, vol. 45, no. 4, pp. 392-398. https://doi.org/10.1038/ng.2561

TY - JOUR

T1 - Genome-wide association studies identify four ER negative-specific breast cancer risk loci

AU - Garcia-Closas, Montserrat

AU - Couch, Fergus J

AU - Lindstrom, Sara

AU - Michailidou, Kyriaki

AU - Schmidt, Marjanka K.

AU - Brook, Mark N.

AU - Orr, Nick

AU - Rhie, Suhn Kyong

AU - Riboli, Elio B

AU - Feigelson, Heather Spencer

AU - Le Marchand, Loic

AU - Buring, Julie E

AU - Eccles, Diana M

AU - Miron, Penelope

AU - Fasching, Peter A.

AU - Brauch, Hiltrud

AU - Chang-Claude, Jenny

AU - Carpenter, Jane

AU - Godwin, Andrew K.

AU - Nevanlinna, Heli

AU - Giles, Graham G.

AU - Southey, Melissa C.

AU - McLean, Catriona

AU - Makalic, Enes

PY - 2013/4

Y1 - 2013/4

N2 - Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10-12 and LGR6, P = 1.4 × 10-8), 2p24.1 (P = 4.6 × 10-8) and 16q12.2 (FTO, P = 4.0 × 10-8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

AB - Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10-12 and LGR6, P = 1.4 × 10-8), 2p24.1 (P = 4.6 × 10-8) and 16q12.2 (FTO, P = 4.0 × 10-8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

UR - https://www.scopus.com/pages/publications/84875701351

U2 - 10.1038/ng.2561

DO - 10.1038/ng.2561

M3 - Article

C2 - 23535733

AN - SCOPUS:84875701351

SN - 1061-4036

VL - 45

SP - 392

EP - 398

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

Genome-wide association studies identify four ER negative-specific breast cancer risk loci

Abstract

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