Abstract
GATA-binding protein 3 (GATA3) is a transcription factor that is crucial to mammary gland morphogenesis and differentiation of progenitor cells, and has been suggested to have a tumor suppressor function. The rs570613 single nucleotide polymorphism (SNP) in intron 4 of GATA3 was previously found to be associated with a reduction in breast cancer risk in the Cancer Genetic Markers of Susceptibility project and in pooled analysis of two case-control studies from Norway and Poland (P trend = 0.004), with some evidence for a stronger association with estrogen receptor (ER) negative tumours [Garcia-Closas M et al. (2007) Cancer Epidemiol Biomarkers Prev 16:2269–2275]. We genotyped GATA3 rs570613 in 6,388 cases and 4,995 controls from the Breast Cancer Association Consortium (BCAC) and 5,617 BRCA1 and BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). We found no association between this SNP and breast cancer risk in BCAC cases overall (ORper-allele = 1.00, 95% CI 0.94–1.05), in ER negative BCAC cases (ORper-allele = 1.02, 95% CI 0.91–1.13), in BRCA1 mutation carriers RRper-allele = 0.99, 95% CI 0.90–1.09) or BRCA2 mutation carriers (RRper-allele = 0.93, 95% CI 0.80–1.07). We conclude that there is no evidence that either GATA3 rs570613, or any variant in strong linkage disequilibrium with it, is associated with breast cancer risk in women.
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Acknowledgments
We wish to thank Claudine Isaacs for the samples from Georgetown; Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded by NHMRC grants 145684, 288704 and 454508) for their contributions to this resourcekConFab; the AOCS Management Group (D. Bowtell, G. Chenevix-Trench, A. deFazio, D. Gertig, A. Green, P. Webb), all the clinical and scientific collaborators of AOCS (http://www.aocstudy.org/), the project staff, and collaborating institutions; Maggie Angelakos, Judi Maskiell and Gillian Dite (ABCFS); RN Hanna Jäntti for help with the patient data and the Finnish Cancer registry for the cancer data (HEBCS); Anne-Catherine Spiess and Georg Pfeiler (MUV); Betsy Bove, Mary Daly, John Malick, Beth Stearman, JoEllen Weaver (FCCC); Gisella Lombardi (PBCS); Beate Pesch, Volker Harth and Thomas Brüning for recruitment of GENICA study subjects and collection of epidemiological data.
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The authors S. E. Johnatty and F. J. Couch contributed equally to this work.
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Appendix
The Epidemiological study of BRCA1 & BRCA2 mutation carriers (EMBRACE) collaborating centres are: Coordinating Centre, Cambridge (Dr. Susan Peock; Mrs. Margaret Cook); North of Scotland Regional Genetics Service, Aberdeen (Prof. Neva Haites: Dr. Helen Gregory); Northern Ireland Regional Genetics Service, Belfast (Prof. Patrick Morrison); West Midlands Regional Clinical Genetics Service, Birmingham (Dr. Trevor Cole; Dr. Carole McKeown, Lucy Burgess); South West Regional Genetics Service, Bristol (Dr. Alan Donaldson); East Anglian Regional Genetics Service, Cambridge (Dr. Joan Paterson); Medical Genetics Services for Wales, Cardiff (Dr. Alexandra Murray; Dr. Mark Rogers; Dr. Emma McCann); Dublin and National Centre for Medical Genetics, Dublin (Dr. John Kennedy; Prof. Peter Daly; Dr. David Barton); St. James’s Hospital, South East of Scotland Regional Genetics Service, Edinburgh (Dr. Mary Porteous; Prof. Michael Steel); Peninsula Clinical Genetics Service, Exeter (Dr. Carole Brewer; Dr. Julia Rankin) West of Scotland Regional Genetics Service, Glasgow (Dr. Rosemarie Davidson; Dr. Victoria Murday, Nicola Bradshaw, Catherine Watt, Lesley Snadden, Mark Longmuir); South East Thames Regional Genetics Service, Guys Hospital London (Dr. Louise Izatt; Dr. Gabriella Pichert, Caroline Langman); North West Thames Regional Genetics Service, Harrow (Dr. Huw Dorkins); Leicestershire Clinical Genetics Service, Leicester (Dr. Julian Barwell); Yorkshire Regional Genetics Service, Leeds (Prof. Timothy Bishop; Dr. Carol Chu); Merseyside and Cheshire Clinical Genetics Service, Liverpool (Dr. Ian Ellis); Manchester Regional Genetics Service, Manchester (Prof. Gareth Evans, Dr. Fiona Lalloo; Mr. Andrew Shenton); North East Thames Regional Genetics Service, NE Thames (Dr. Alison Male; Dr. Anne Robinson); Nottingham Centre for Medical Genetics, Nottingham (Dr. Carol Gardiner); Northern Clinical Genetics Service, Newcastle (Dr. Fiona Douglas; Prof. John Burn); Oxford Regional Genetics Service, Oxford (Dr. Lucy Side; Dr. Lisa Walker; Ms. Sarah Durell); Cancer Genetics Unit, Royal Marsden NHS Foundation Trust (Dr. Ros Eeles, Dr. Susan Shanley, Prof. Naz Rahman, Prof. Richard Houlston, Elizabeth Bancroft, Lucia D’Mello, Audrey Ardern-Jones); North Trent Clinical Genetics Service, Sheffield (Dr. Jackie Cook; Dr. Oliver Quarrell); South West Thames Regional Genetics Service, London (Prof. Shirley Hodgson, Sheila Goff); Wessex Clinical Genetics Service, Southampton (Prof. Diana Eccles; Dr. Anneke Lucassen);. DFE is the PI of the study.
The Swedish BRCA1 and BRCA2 study (SWE-BRCA) collaborators are Per Karlsson, Margareta Nordling, Annika Bergman, and Zakaria Einbeigi, Gothenburg, Sahlgrenska University Hospital; Marie Stenmark-Askmalm and Sigrun Liedgren, Linkoping University Hospital; Ake Borg, Niklas Loman, Hakan Olsson, Ulf Kristoffersson, Helena Jernstrom, and Katja Backenhorn, Lund University Hospital; Annika Lindblom, Brita Arver, Anna von Wachenfeldt, Annelie Liljegren, Gisela Barbany-Bustinza, and Johanna Rantala, Stockholm, Karolinska University Hospital; Henrik Gronberg, Eva-Lena Stattin, and Monica Emanuelsson, Umea University Hospital; Hans Bostrom, Richard Rosenquist Brandell, and Niklas Dahl, Uppsala University Hospital.
The Hereditary Breast and Ovarian Cancer Working Group Netherlands (HEBON) collaborating centres are: Netherlands Cancer Institute, Amsterdam: Frans Hogervorst, Anouk Pijpe, Senno Verhoef, Flora van Leeuwen, Laura van ‘t Veer, Matti Rookus; Erasmus University Medical Centre, Rotterdam: Ans van den Ouweland, Mieke Schutte, Margriet Collée, Agnes Jager, Maartje Hooning, Caroline Seynaeve; Leiden University Medical Centre, Leiden: Juul Wijnen, Christi van Asperen, Peter Devilee; Radboud University Nijmegen Medical Centre, Nijmegen: Marjolijn Ligtenberg, Nicoline Hoogerbrugge; University Medical Centre Utrecht, Utrecht: Rob van der Luijt, Margreet Ausems; Amsterdam Medical Centre: Cora Aalfs, Theo van Os; VU University Medical Centre, Amsterdam: Hans Gille, Hanne Meijers-Heijboer; University Hospital Maastricht, Maastricht: Rien Blok, Encarna Gomez-Garcia.
FJC, ZF and RT and the MAYO study were supported in part by U.S. National Institutes of Health grants CA122340 and CA128978 and an award from the Breast Cancer Research Foundation. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. AOCS was funded by U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, the Cancer Council Tasmania and Cancer Foundation of Western Australia (AOCS study). The ABCFS was supported by the National Health and Medical Research Council (NHMRC) of Australia (#145604), the U.S. National Institutes of Health (RO1 CA102740-01A2) and by the National Cancer Institute, National Institutes of Health under RFA # CA-95-011 through cooperative agreements with members of the Breast Cancer Family Registry (Breast CFR) and PIs “Cancer Care Ontario (UO1 CA69467)”, “Columbia University (U01 CA69398)”, “Fox Chase Cancer Center (U01 CA69631)”, “Huntsman Cancer Institute (U01 CA69446)”, “Northern California Cancer Center (U01 CA69417)”, “University of Melbourne (U01 CA69638)”. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of collaborating centers in the Breast CFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the Breast CFR. The Australian Breast Cancer Family Study was initially supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation. SWE-BRCA is supported by grants from the Swedish Cancer Society and Swedish County Council. The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (110663), Finnish Cancer Society and the Sigrid Juselius Foundation; This work was supported in part by the Fox Chase Cancer Center Ovarian Cancer SPORE, P50 CA83638, and the Eileen Stein-Jacoby Fund. CIMBA data management” is funded by CR-UK. PBCS is supported by Fondazione Cassa di Risparmio. The GENICA study was supported by the German Human Genome Project and funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114. Genotyping analysis was supported by the Robert Bosch Foundation of Medical Research, Stuttgart, Germany. The HEBON study and Anouk Pijpe are funded by the Dutch Cancer Society grant NKI2004-3088, NKI 2007-3756. GCT, JLH, MS and PW are supported by the NHMRC. Antonis Antoniou, Lesley McGuffog, Margaret Cook, Susan Peock and EMBRACE are funded by Cancer Research–UK. We would also like to thank the 17,100 women who participated in these studies.
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Johnatty, S.E., Couch, F.J., Fredericksen, Z. et al. No evidence that GATA3 rs570613 SNP modifies breast cancer risk. Breast Cancer Res Treat 117, 371–379 (2009). https://doi.org/10.1007/s10549-008-0257-1
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DOI: https://doi.org/10.1007/s10549-008-0257-1