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 Riboli; Heather S Feigelson; Loic Le Marchand; Julie E Buring; Diana Eccles; Penelope Miron; Peter A Fasching; Hiltrud Brauch; Jenny Chang-Claude; Jane Carpenter; Andrew K Godwin; Heli Nevanlinna; Graham G Giles; Angela Cox; John L Hopper; Manjeet K Bolla; Qin Wang; Joe Dennis; Ed Dicks; Will J Howat; Nils Schoof; Stig E Bojesen; Diether Lambrechts; Annegien Broeks; Irene L Andrulis; Pascal Guénel; Barbara Burwinkel; Elinor J Sawyer; Antoinette Hollestelle; Olivia Fletcher; Robert Winqvist; Hermann Brenner; Arto Mannermaa; Ute Hamann; Alfons Meindl; Annika Lindblom; Wei Zheng; Peter Devillee; Mark S Goldberg; Jan Lubinski; Vessela Kristensen; Børge G Nordestgaard; Gene ENvironmental Interaction and breast CAncer (GENICA) Network

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 Riboli, Heather S Feigelson, Loic Le Marchand, Julie E Buring, Diana Eccles, Penelope Miron, Peter A Fasching, Hiltrud Brauch, Jenny Chang-Claude, Jane Carpenter, Andrew K Godwin, Heli NevanlinnaGraham G Giles, Angela Cox, John L Hopper, Manjeet K Bolla, Qin Wang, Joe Dennis, Ed Dicks, Will J Howat, Nils Schoof, Stig E Bojesen, Diether Lambrechts, Annegien Broeks, Irene L Andrulis, Pascal Guénel, Barbara Burwinkel, Elinor J Sawyer, Antoinette Hollestelle, Olivia Fletcher, Robert Winqvist, Hermann Brenner, Arto Mannermaa, Ute Hamann, Alfons Meindl, Annika Lindblom, Wei Zheng, Peter Devillee, Mark S Goldberg, Jan Lubinski, Vessela Kristensen, Børge G Nordestgaard, Gene ENvironmental Interaction and breast CAncer (GENICA) Network

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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
Journal	Nature Genetics
Volume	45
Issue number	4
Pages (from-to)	392-8, 398e1-2
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.2561
Publication status	Published - Apr 2013

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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., Feigelson, H. S., Le Marchand, L., Buring, J. E., Eccles, D., Miron, P., Fasching, P. A., Brauch, H., Chang-Claude, J., Carpenter, J., Godwin, A. K., ... Gene ENvironmental Interaction and breast CAncer (GENICA) Network (2013). Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nature Genetics, 45(4), 392-8, 398e1-2. https://doi.org/10.1038/ng.2561

Garcia-Closas, M, Couch, FJ, Lindstrom, S, Michailidou, K, Schmidt, MK, Brook, MN, Orr, N, Rhie, SK, Riboli, E, Feigelson, HS, Le Marchand, L, Buring, JE, Eccles, D, Miron, P, Fasching, PA, Brauch, H, Chang-Claude, J, Carpenter, J, Godwin, AK, Nevanlinna, H, Giles, GG, Cox, A, Hopper, JL, Bolla, MK, Wang, Q, Dennis, J, Dicks, E, Howat, WJ, Schoof, N, Bojesen, SE, Lambrechts, D, Broeks, A, Andrulis, IL, Guénel, P, Burwinkel, B, Sawyer, EJ, Hollestelle, A, Fletcher, O, Winqvist, R, Brenner, H, Mannermaa, A, Hamann, U, Meindl, A, Lindblom, A, Zheng, W, Devillee, P, Goldberg, MS, Lubinski, J, Kristensen, V, Nordestgaard, BG & Gene ENvironmental Interaction and breast CAncer (GENICA) Network 2013, 'Genome-wide association studies identify four ER negative-specific breast cancer risk loci', Nature Genetics, vol. 45, no. 4, pp. 392-8, 398e1-2. https://doi.org/10.1038/ng.2561

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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 Elio Riboli and Feigelson, {Heather S} and {Le Marchand}, Loic and Buring, {Julie E} and Diana Eccles 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 Angela Cox and Hopper, {John L} and Bolla, {Manjeet K} and Qin Wang and Joe Dennis and Ed Dicks and Howat, {Will J} and Nils Schoof and Bojesen, {Stig E} and Diether Lambrechts and Annegien Broeks and Andrulis, {Irene L} and Pascal Gu{\'e}nel and Barbara Burwinkel and Sawyer, {Elinor J} and Antoinette Hollestelle and Olivia Fletcher and Robert Winqvist and Hermann Brenner and Arto Mannermaa and Ute Hamann and Alfons Meindl and Annika Lindblom and Wei Zheng and Peter Devillee and Goldberg, {Mark S} and Jan Lubinski and Vessela Kristensen and Nordestgaard, {B{\o}rge G} and B{\o}rge Nordestgaard",

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doi = "10.1038/ng.2561",

language = "English",

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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

AU - Feigelson, Heather S

AU - Le Marchand, Loic

AU - Buring, Julie E

AU - Eccles, Diana

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 - Cox, Angela

AU - Hopper, John L

AU - Bolla, Manjeet K

AU - Wang, Qin

AU - Dennis, Joe

AU - Dicks, Ed

AU - Howat, Will J

AU - Schoof, Nils

AU - Bojesen, Stig E

AU - Lambrechts, Diether

AU - Broeks, Annegien

AU - Andrulis, Irene L

AU - Guénel, Pascal

AU - Burwinkel, Barbara

AU - Sawyer, Elinor J

AU - Hollestelle, Antoinette

AU - Fletcher, Olivia

AU - Winqvist, Robert

AU - Brenner, Hermann

AU - Mannermaa, Arto

AU - Hamann, Ute

AU - Meindl, Alfons

AU - Lindblom, Annika

AU - Zheng, Wei

AU - Devillee, Peter

AU - Goldberg, Mark S

AU - Lubinski, Jan

AU - Kristensen, Vessela

AU - Nordestgaard, Børge G

AU - Gene ENvironmental Interaction and breast CAncer (GENICA) Network

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.

U2 - 10.1038/ng.2561

DO - 10.1038/ng.2561

M3 - Journal article

C2 - 23535733

SN - 1061-4036

VL - 45

SP - 392-8, 398e1-2

JO - Nature Genetics

JF - Nature Genetics

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