Association of ESR1 gene tagging SNPs with breast cancer risk

Alison M. Dunning; Catherine S. Healey; Caroline Baynes; Ana Teresa Maia; Serena Scollen; Ana Vega; Raquel Rodríguez; Nuno L. Barbosa-Morais; Bruce A.J. Ponder; Yen Ling Low; Sheila Bingham; Christopher A. Haiman; Loic Le Marchand; Annegien Broeks; Marjanka K. Schmidt; John Hopper; Melissa Southey; Matthias W. Beckmann; Peter A. Fasching; Julian Peto; Nichola Johnson; Stig E. Bojesen; Børge Nordestgaard; Roger L. Milne; Javier Benitez; Ute Hamann; Yon Ko; Rita K. Schmutzler; Barbara Burwinkel; Peter Schürmann; Thilo Dörk; Tuomas Heikkinen; Heli Nevanlinna; Annika Lindblom; Sara Margolin; Arto Mannermaa; Veli Matti Kosma; Xiaoqing Chen; Amanda Spurdle; Jenny Change-Claude; Dieter Flesch-Janys; Fergus J. Couch; Janet E. Olson; Gianluca Severi; Laura Baglietto; Anne Lise Børresen-Dale; Vessela Kristensen; David J. Hunter; Susan E. Hankinson; Peter Devilee; Maaike Vreeswijk; Jolanta Lissowska; Louise Brinton; Jianjun Liu; Per Hall; Daehee Kang; Keun Young Yoo; Chen Yang Shen; Jyh Cherng Yu; Hoda Anton-Culver; Argyrios Ziogoas; Alice Sigurdson; Jeff Struewing; Douglas F. Easton; Montserrat Garcia-Closas; Manjeet K. Humphreys; Jonathan Morrison; Paul D.P. Pharoah; Karen A. Pooley; Georgia Chenevix-Trench

doi:10.1093/hmg/ddn429

Association of ESR1 gene tagging SNPs with breast cancer risk

Alison M. Dunning, Catherine S. Healey, Caroline Baynes, Ana Teresa Maia, Serena Scollen, Ana Vega, Raquel Rodríguez, Nuno L. Barbosa-Morais, Bruce A.J. Ponder, Yen Ling Low, Sheila Bingham, Christopher A. Haiman, Loic Le Marchand, Annegien Broeks, Marjanka K. Schmidt, John Hopper, Melissa Southey, Matthias W. Beckmann, Peter A. Fasching, Julian PetoNichola Johnson, Stig E. Bojesen, Børge Nordestgaard, Roger L. Milne, Javier Benitez, Ute Hamann, Yon Ko, Rita K. Schmutzler, Barbara Burwinkel, Peter Schürmann, Thilo Dörk, Tuomas Heikkinen, Heli Nevanlinna, Annika Lindblom, Sara Margolin, Arto Mannermaa, Veli Matti Kosma, Xiaoqing Chen, Amanda Spurdle, Jenny Change-Claude, Dieter Flesch-Janys, Fergus J. Couch, Janet E. Olson, Gianluca Severi, Laura Baglietto, Anne Lise Børresen-Dale, Vessela Kristensen, David J. Hunter, Susan E. Hankinson, Peter Devilee, Maaike Vreeswijk, Jolanta Lissowska, Louise Brinton, Jianjun Liu, Per Hall, Daehee Kang, Keun Young Yoo, Chen Yang Shen, Jyh Cherng Yu, Hoda Anton-Culver, Argyrios Ziogoas, Alice Sigurdson, Jeff Struewing, Douglas F. Easton, Montserrat Garcia-Closas, Manjeet K. Humphreys, Jonathan Morrison, Paul D.P. Pharoah, Karen A. Pooley, Georgia Chenevix-Trench

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

74 Scopus citations

Abstract

We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55 000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant associations were revealed. SNP rs3020314, tagging a region of ESR1 intron 4, is associated with an increase in breast cancer susceptibility with a dominant mode of action in European populations. Carriers of the c -allele have an odds ratio (OR) of 1.05 [95% Confidence Intervals (CI) 1.02-1.09] relative to t -allele homozygotes, P = 0.004. There is significant heterogeneity between studies, P = 0.002. The increased risk appears largely confined to oestrogen receptor-positive tumour risk. The region tagged by SNP rs3020314 contains sequence that is more highly conserved across mammalian species than the rest of intron 4, and it may subtly alter the ratio of two mRNA splice forms.

Original language	English (US)
Pages (from-to)	1131-1139
Number of pages	9
Journal	Human molecular genetics
Volume	18
Issue number	6
DOIs	https://doi.org/10.1093/hmg/ddn429
State	Published - 2009

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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10.1093/hmg/ddn429

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Dunning, A. M., Healey, C. S., Baynes, C., Maia, A. T., Scollen, S., Vega, A., Rodríguez, R., Barbosa-Morais, N. L., Ponder, B. A. J., Low, Y. L., Bingham, S., Haiman, C. A., Le Marchand, L., Broeks, A., Schmidt, M. K., Hopper, J., Southey, M., Beckmann, M. W., Fasching, P. A., ... Chenevix-Trench, G. (2009). Association of ESR1 gene tagging SNPs with breast cancer risk. Human molecular genetics, 18(6), 1131-1139. https://doi.org/10.1093/hmg/ddn429

Dunning, AM, Healey, CS, Baynes, C, Maia, AT, Scollen, S, Vega, A, Rodríguez, R, Barbosa-Morais, NL, Ponder, BAJ, Low, YL, Bingham, S, Haiman, CA, Le Marchand, L, Broeks, A, Schmidt, MK, Hopper, J, Southey, M, Beckmann, MW, Fasching, PA, Peto, J, Johnson, N, Bojesen, SE, Nordestgaard, B, Milne, RL, Benitez, J, Hamann, U, Ko, Y, Schmutzler, RK, Burwinkel, B, Schürmann, P, Dörk, T, Heikkinen, T, Nevanlinna, H, Lindblom, A, Margolin, S, Mannermaa, A, Kosma, VM, Chen, X, Spurdle, A, Change-Claude, J, Flesch-Janys, D, Couch, FJ , Olson, JE, Severi, G, Baglietto, L, Børresen-Dale, AL, Kristensen, V, Hunter, DJ, Hankinson, SE, Devilee, P, Vreeswijk, M, Lissowska, J, Brinton, L, Liu, J, Hall, P, Kang, D, Yoo, KY, Shen, CY, Yu, JC, Anton-Culver, H, Ziogoas, A, Sigurdson, A, Struewing, J, Easton, DF, Garcia-Closas, M, Humphreys, MK, Morrison, J, Pharoah, PDP, Pooley, KA & Chenevix-Trench, G 2009, 'Association of ESR1 gene tagging SNPs with breast cancer risk', Human molecular genetics, vol. 18, no. 6, pp. 1131-1139. https://doi.org/10.1093/hmg/ddn429

@article{5662f031888b44efbabb276d9364acf8,

title = "Association of ESR1 gene tagging SNPs with breast cancer risk",

abstract = "We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55 000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant associations were revealed. SNP rs3020314, tagging a region of ESR1 intron 4, is associated with an increase in breast cancer susceptibility with a dominant mode of action in European populations. Carriers of the c -allele have an odds ratio (OR) of 1.05 [95% Confidence Intervals (CI) 1.02-1.09] relative to t -allele homozygotes, P = 0.004. There is significant heterogeneity between studies, P = 0.002. The increased risk appears largely confined to oestrogen receptor-positive tumour risk. The region tagged by SNP rs3020314 contains sequence that is more highly conserved across mammalian species than the rest of intron 4, and it may subtly alter the ratio of two mRNA splice forms.",

author = "Dunning, {Alison M.} and Healey, {Catherine S.} and Caroline Baynes and Maia, {Ana Teresa} and Serena Scollen and Ana Vega and Raquel Rodr{\'i}guez and Barbosa-Morais, {Nuno L.} and Ponder, {Bruce A.J.} and Low, {Yen Ling} and Sheila Bingham and Haiman, {Christopher A.} and {Le Marchand}, Loic and Annegien Broeks and Schmidt, {Marjanka K.} and John Hopper and Melissa Southey and Beckmann, {Matthias W.} and Fasching, {Peter A.} and Julian Peto and Nichola Johnson and Bojesen, {Stig E.} and B{\o}rge Nordestgaard and Milne, {Roger L.} and Javier Benitez and Ute Hamann and Yon Ko and Schmutzler, {Rita K.} and Barbara Burwinkel and Peter Sch{\"u}rmann and Thilo D{\"o}rk and Tuomas Heikkinen and Heli Nevanlinna and Annika Lindblom and Sara Margolin and Arto Mannermaa and Kosma, {Veli Matti} and Xiaoqing Chen and Amanda Spurdle and Jenny Change-Claude and Dieter Flesch-Janys and Couch, {Fergus J.} and Olson, {Janet E.} and Gianluca Severi and Laura Baglietto and B{\o}rresen-Dale, {Anne Lise} and Vessela Kristensen and Hunter, {David J.} and Hankinson, {Susan E.} and Peter Devilee and Maaike Vreeswijk and Jolanta Lissowska and Louise Brinton and Jianjun Liu and Per Hall and Daehee Kang and Yoo, {Keun Young} and Shen, {Chen Yang} and Yu, {Jyh Cherng} and Hoda Anton-Culver and Argyrios Ziogoas and Alice Sigurdson and Jeff Struewing and Easton, {Douglas F.} and Montserrat Garcia-Closas and Humphreys, {Manjeet K.} and Jonathan Morrison and Pharoah, {Paul D.P.} and Pooley, {Karen A.} and Georgia Chenevix-Trench",

note = "Funding Information: ABCS acknowledges Laura Van{\textquoteright}t Veer, Rob Tollenaar, Flora van Leeuwen and other members of the BOSOM project, the support of Dr H.B. Bueno-de-Mesquita for organizing the release of control DNA, and financial support by the Dutch Cancer Society (NKI 2001-2423 and 2007-3839), the Cancer Genomics Center (Dutch Genomics Initiative) and the Ministry of Health, Welfare and Sports of The Netherlands. ABCFS is part of the Breast Cancer Family Registry supported by the National Cancer Institute, National Institutes of Health under RFA-CA-06-503 and R01-CA121245-01A2, and through cooperative agreements with members of the Breast Cancer Family Registry and P.I.s, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417) and University of Melbourne (U01 CA69638). J.H. is an Australia Fellow of the National Health and Medical Research Council (NHMRC) and Melissa Southey is an NHMRC Senior Research Fellow. BBCS—the British Breast Cancer Study and the Mammography Oestrogens and Growth Factors Study are funded by Cancer Research-UK and Breakthrough Breast Cancer. We acknowledge NHS funding to the NIHR Biomedical Research Centre. CGPS was funded by the Chief Physician Johan Boserup and Lise Boserups Fund the Copenhagen County Research Fund and the Danish Medical Research Council. CNIO-BCS was partially funded by the Genome Spain Foundation and the Marato Foundation. GENICA was supported by the German Human Genome Project and funded by the Federal Ministry of Education and Research (BMBF) grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114. We thank Hiltrud Brauch for conceptual design and coordination of the study, Beate Pesch, Volker Harth and Thomas Br{\"u}ning for patient recruitment and collection of epidemiologic data, as well as Susanne Haas and Hans-Peter Fischer for histopathological data. GC-HBOC was supported by the Deutsche Kreb-shilfe. We thank Claus R. Bartram for patient recruitment and Sandrine Tchatchou for genotyping. HABCS acknowledges the support of Profs. Michael Bremer and Johann Hinrich Kar-stens at the Clinics of Radiation Oncology and of Prof. Peter Hillemanns at the Clinics of Obstetrics and Gynaecology, Hannover Medical School, for providing patient samples and infrastructure. HEBCS was supported by the Academy of Finland (110663), Helsinki University Central Hospital Research Fund, the Sigrid Juselius Fund and the Finnish Cancer Society. We thank Kati K{\"a}mpj{\"a}rvi for her contribution to the molecular analyses and Drs Kirsimari Aaltonen, Carl Blomqvist and Kristiina Aittom{\"a}ki for their help in patient sample and data collection. KARBAC was supported by the Swedish Cancer Society, the Gustav V Jubilee Foundation, and the Bert von Kantzow foundation. kConFab is supported by the National Breast Cancer Foundation, the National Health and Medical Research Council of Australia and the Cancer Councils of Queensland, New South Wales, Western Australia, South Australia and Victoria. We thank kConFab nurses, staff of the Familial Cancer Clinics, Heather Thorne, Eveline Niedermayr, Helene Holland and Gillian Dite for their contribution and Study of kConFab [funded by the National Health and Medical Research Council of Australia (NHMRC grants 145684 and 288704)] for supplying some data. AOCS, which provided control samples only for the kConFab study, was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, the National Health and Medical Research Council of Australia (199600), the Cancer Council Tasmania and Cancer Foundation of Western Australia. The AOCS Management Group members include David Bowtell, Adele Green, Penny Webb, Anna DeFazio and Dorota Gertig. The genotyping and analysis were supported by grants from the National Health and Medical Research Council (NHMRC). We thank Jonathan Beesley for laboratory assistance. Georgia Chenevix-Trench is an NHMRC Senior Principal Research Fellow. MARIE was supported by the Deutsche Krebshilfe e.V. (Grant number 70-2892-Br I) and the German Cancer Research Center (DKFZ). We thank Dr Tracy Slanger and Elke Mutschel-knauss for organization and conduct of the field work and Dr Ramona Salazar for the genotyping and Ursula Eilber, Sabine Behrens and Belinda Kaspereit for competent technical support. MCBCS was supported by NIH/NCI Breast Cancer SPORE P50 CA116201, NIH CA122340 and U.S. Department of Defense grant W81XWH-04-1-0588. MCCS is supported by the Australian National Health and Medical Research Council (grants 209057, 251533, 396414, 504711). Cohort recruitment and follow-up is funded by The Cancer Council Victoria. We want to thank Letitia Smith for her contribution to the genotyp-ing. NHS was funded by the National Institutes of Health through CA098233, CA065725 and UO1-CA98233. We thank the NHS investigators, staff and participants. ORIGO was funded by the Dutch Cancer Society and coordinated by Peter Devilee, Jan Klijn and Rob Tollenaar; We thank Jannet Blom,Elly Krol-Warmerdam and Petra Huijts for patient recruitment and collection of clinical data. PBCS thank Stephen Chanock from the Advanced Technology Center and the Division of Cancer Epidemiology and Genetics, Mark Sherman from the Division of Cancer Epidemiology and Genetics, NCI, USA; N. Szeszenia-Dabrowska and Beata Peplonska of the Nofer Institute of Occupational Medicine; and W. Zatonski of the Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, 02-781 Warsaw, Poland for their contribution to the Polish Breast Cancer Study. The content of this manuscript does not necessarily reflect the views or policies of the NCI or any of the collaborating centers in the CFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. SASBAC thank all the subjects who participated. We also give special thanks to Li Yuqing and Carine Bonnard for performing genotyping analysis. This work was funded by the Agency for Science & Technology and Research of Singapore (A*STAR), the National Institute of Health (grant number R01 CA 104021), and the Susan J. Kommen Foundation. SEARCH owe particular thanks to the EPIC Management team for access to control DNA; Ms Inma Spiteri for polysomal RNA, Prof. Carlos Caldas for tumour samples and the Eastern Cancer Registry and Intelligence Unit for data. We would like to acknowledge the support of The University of Cambridge, Hutchison Whampoa Ltd and Cancer Research-UK. A.M.D. is supported by CR-UK and P.D.P.P. is a Senior Clinical Research Fellow of CR-UK.",

year = "2009",

doi = "10.1093/hmg/ddn429",

language = "English (US)",

volume = "18",

pages = "1131--1139",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - Association of ESR1 gene tagging SNPs with breast cancer risk

AU - Dunning, Alison M.

AU - Healey, Catherine S.

AU - Baynes, Caroline

AU - Maia, Ana Teresa

AU - Scollen, Serena

AU - Vega, Ana

AU - Rodríguez, Raquel

AU - Barbosa-Morais, Nuno L.

AU - Ponder, Bruce A.J.

AU - Low, Yen Ling

AU - Bingham, Sheila

AU - Haiman, Christopher A.

AU - Le Marchand, Loic

AU - Broeks, Annegien

AU - Schmidt, Marjanka K.

AU - Hopper, John

AU - Southey, Melissa

AU - Beckmann, Matthias W.

AU - Fasching, Peter A.

AU - Peto, Julian

AU - Johnson, Nichola

AU - Bojesen, Stig E.

AU - Nordestgaard, Børge

AU - Milne, Roger L.

AU - Benitez, Javier

AU - Hamann, Ute

AU - Ko, Yon

AU - Schmutzler, Rita K.

AU - Burwinkel, Barbara

AU - Schürmann, Peter

AU - Dörk, Thilo

AU - Heikkinen, Tuomas

AU - Nevanlinna, Heli

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Mannermaa, Arto

AU - Kosma, Veli Matti

AU - Chen, Xiaoqing

AU - Spurdle, Amanda

AU - Change-Claude, Jenny

AU - Flesch-Janys, Dieter

AU - Couch, Fergus J.

AU - Olson, Janet E.

AU - Severi, Gianluca

AU - Baglietto, Laura

AU - Børresen-Dale, Anne Lise

AU - Kristensen, Vessela

AU - Hunter, David J.

AU - Hankinson, Susan E.

AU - Devilee, Peter

AU - Vreeswijk, Maaike

AU - Lissowska, Jolanta

AU - Brinton, Louise

AU - Liu, Jianjun

AU - Hall, Per

AU - Kang, Daehee

AU - Yoo, Keun Young

AU - Shen, Chen Yang

AU - Yu, Jyh Cherng

AU - Anton-Culver, Hoda

AU - Ziogoas, Argyrios

AU - Sigurdson, Alice

AU - Struewing, Jeff

AU - Easton, Douglas F.

AU - Garcia-Closas, Montserrat

AU - Humphreys, Manjeet K.

AU - Morrison, Jonathan

AU - Pharoah, Paul D.P.

AU - Pooley, Karen A.

AU - Chenevix-Trench, Georgia

N1 - Funding Information: ABCS acknowledges Laura Van’t Veer, Rob Tollenaar, Flora van Leeuwen and other members of the BOSOM project, the support of Dr H.B. Bueno-de-Mesquita for organizing the release of control DNA, and financial support by the Dutch Cancer Society (NKI 2001-2423 and 2007-3839), the Cancer Genomics Center (Dutch Genomics Initiative) and the Ministry of Health, Welfare and Sports of The Netherlands. ABCFS is part of the Breast Cancer Family Registry supported by the National Cancer Institute, National Institutes of Health under RFA-CA-06-503 and R01-CA121245-01A2, and through cooperative agreements with members of the Breast Cancer Family Registry and P.I.s, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417) and University of Melbourne (U01 CA69638). J.H. is an Australia Fellow of the National Health and Medical Research Council (NHMRC) and Melissa Southey is an NHMRC Senior Research Fellow. BBCS—the British Breast Cancer Study and the Mammography Oestrogens and Growth Factors Study are funded by Cancer Research-UK and Breakthrough Breast Cancer. We acknowledge NHS funding to the NIHR Biomedical Research Centre. CGPS was funded by the Chief Physician Johan Boserup and Lise Boserups Fund the Copenhagen County Research Fund and the Danish Medical Research Council. CNIO-BCS was partially funded by the Genome Spain Foundation and the Marato Foundation. GENICA was supported by the German Human Genome Project and funded by the Federal Ministry of Education and Research (BMBF) grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114. We thank Hiltrud Brauch for conceptual design and coordination of the study, Beate Pesch, Volker Harth and Thomas Brüning for patient recruitment and collection of epidemiologic data, as well as Susanne Haas and Hans-Peter Fischer for histopathological data. GC-HBOC was supported by the Deutsche Kreb-shilfe. We thank Claus R. Bartram for patient recruitment and Sandrine Tchatchou for genotyping. HABCS acknowledges the support of Profs. Michael Bremer and Johann Hinrich Kar-stens at the Clinics of Radiation Oncology and of Prof. Peter Hillemanns at the Clinics of Obstetrics and Gynaecology, Hannover Medical School, for providing patient samples and infrastructure. HEBCS was supported by the Academy of Finland (110663), Helsinki University Central Hospital Research Fund, the Sigrid Juselius Fund and the Finnish Cancer Society. We thank Kati Kämpjärvi for her contribution to the molecular analyses and Drs Kirsimari Aaltonen, Carl Blomqvist and Kristiina Aittomäki for their help in patient sample and data collection. KARBAC was supported by the Swedish Cancer Society, the Gustav V Jubilee Foundation, and the Bert von Kantzow foundation. kConFab is supported by the National Breast Cancer Foundation, the National Health and Medical Research Council of Australia and the Cancer Councils of Queensland, New South Wales, Western Australia, South Australia and Victoria. We thank kConFab nurses, staff of the Familial Cancer Clinics, Heather Thorne, Eveline Niedermayr, Helene Holland and Gillian Dite for their contribution and Study of kConFab [funded by the National Health and Medical Research Council of Australia (NHMRC grants 145684 and 288704)] for supplying some data. AOCS, which provided control samples only for the kConFab study, was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, the National Health and Medical Research Council of Australia (199600), the Cancer Council Tasmania and Cancer Foundation of Western Australia. The AOCS Management Group members include David Bowtell, Adele Green, Penny Webb, Anna DeFazio and Dorota Gertig. The genotyping and analysis were supported by grants from the National Health and Medical Research Council (NHMRC). We thank Jonathan Beesley for laboratory assistance. Georgia Chenevix-Trench is an NHMRC Senior Principal Research Fellow. MARIE was supported by the Deutsche Krebshilfe e.V. (Grant number 70-2892-Br I) and the German Cancer Research Center (DKFZ). We thank Dr Tracy Slanger and Elke Mutschel-knauss for organization and conduct of the field work and Dr Ramona Salazar for the genotyping and Ursula Eilber, Sabine Behrens and Belinda Kaspereit for competent technical support. MCBCS was supported by NIH/NCI Breast Cancer SPORE P50 CA116201, NIH CA122340 and U.S. Department of Defense grant W81XWH-04-1-0588. MCCS is supported by the Australian National Health and Medical Research Council (grants 209057, 251533, 396414, 504711). Cohort recruitment and follow-up is funded by The Cancer Council Victoria. We want to thank Letitia Smith for her contribution to the genotyp-ing. NHS was funded by the National Institutes of Health through CA098233, CA065725 and UO1-CA98233. We thank the NHS investigators, staff and participants. ORIGO was funded by the Dutch Cancer Society and coordinated by Peter Devilee, Jan Klijn and Rob Tollenaar; We thank Jannet Blom,Elly Krol-Warmerdam and Petra Huijts for patient recruitment and collection of clinical data. PBCS thank Stephen Chanock from the Advanced Technology Center and the Division of Cancer Epidemiology and Genetics, Mark Sherman from the Division of Cancer Epidemiology and Genetics, NCI, USA; N. Szeszenia-Dabrowska and Beata Peplonska of the Nofer Institute of Occupational Medicine; and W. Zatonski of the Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, 02-781 Warsaw, Poland for their contribution to the Polish Breast Cancer Study. The content of this manuscript does not necessarily reflect the views or policies of the NCI or any of the collaborating centers in the CFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. SASBAC thank all the subjects who participated. We also give special thanks to Li Yuqing and Carine Bonnard for performing genotyping analysis. This work was funded by the Agency for Science & Technology and Research of Singapore (A*STAR), the National Institute of Health (grant number R01 CA 104021), and the Susan J. Kommen Foundation. SEARCH owe particular thanks to the EPIC Management team for access to control DNA; Ms Inma Spiteri for polysomal RNA, Prof. Carlos Caldas for tumour samples and the Eastern Cancer Registry and Intelligence Unit for data. We would like to acknowledge the support of The University of Cambridge, Hutchison Whampoa Ltd and Cancer Research-UK. A.M.D. is supported by CR-UK and P.D.P.P. is a Senior Clinical Research Fellow of CR-UK.

PY - 2009

Y1 - 2009

N2 - We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55 000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant associations were revealed. SNP rs3020314, tagging a region of ESR1 intron 4, is associated with an increase in breast cancer susceptibility with a dominant mode of action in European populations. Carriers of the c -allele have an odds ratio (OR) of 1.05 [95% Confidence Intervals (CI) 1.02-1.09] relative to t -allele homozygotes, P = 0.004. There is significant heterogeneity between studies, P = 0.002. The increased risk appears largely confined to oestrogen receptor-positive tumour risk. The region tagged by SNP rs3020314 contains sequence that is more highly conserved across mammalian species than the rest of intron 4, and it may subtly alter the ratio of two mRNA splice forms.

AB - We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55 000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant associations were revealed. SNP rs3020314, tagging a region of ESR1 intron 4, is associated with an increase in breast cancer susceptibility with a dominant mode of action in European populations. Carriers of the c -allele have an odds ratio (OR) of 1.05 [95% Confidence Intervals (CI) 1.02-1.09] relative to t -allele homozygotes, P = 0.004. There is significant heterogeneity between studies, P = 0.002. The increased risk appears largely confined to oestrogen receptor-positive tumour risk. The region tagged by SNP rs3020314 contains sequence that is more highly conserved across mammalian species than the rest of intron 4, and it may subtly alter the ratio of two mRNA splice forms.

UR - http://www.scopus.com/inward/record.url?scp=61849132987&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61849132987&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddn429

DO - 10.1093/hmg/ddn429

M3 - Article

C2 - 19126777

AN - SCOPUS:61849132987

SN - 0964-6906

VL - 18

SP - 1131

EP - 1139

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 6

ER -

Association of ESR1 gene tagging SNPs with breast cancer risk

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