No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A multi-center cohort study

Timothy R. Rebbeck; Antonis C. Antoniou; Trinidad Caldes Llopis; Heli Nevanlinna; Kristiina Aittomäki; Jacques Simard; Amanda B. Spurdle; Fergus J. Couch; Lutecia H.Mateus Pereira; Mark H. Greene; Irene L. Andrulis; Boris Pasche; Virginia Kaklamani; Ute Hamann; Csilla Szabo; Susan Peock; Margaret Cook; Patricia A. Harrington; Alan Donaldson; Allison M. Male; Carol Anne Gardiner; Helen Gregory; Lucy E. Side; Anne C. Robinson; Louise Emmerson; Ian Ellis; Jean Philippe Peyrat; Joëlle Fournier; Philippe Vennin; Claude Adenis; Danièle Muller; Jean Pierre Fricker; Michel Longy; Olga M. Sinilnikova; Dominique Stoppa-Lyonnet; Rita K. Schmutzler; Beatrix Versmold; Christoph Engel; Alfons Meindl; Karin Kast; Dieter Schaefer; Ursula G. Froster; Georgia Chenevix-Trench; Douglas F. Easton

doi:10.1007/s10549-008-0064-8

No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A multi-center cohort study

Timothy R. Rebbeck, Antonis C. Antoniou, Trinidad Caldes Llopis, Heli Nevanlinna, Kristiina Aittomäki, Jacques Simard, Amanda B. Spurdle, Fergus J. Couch, Lutecia H.Mateus Pereira, Mark H. Greene, Irene L. Andrulis, Boris Pasche, Virginia Kaklamani, Ute Hamann, Csilla Szabo, Susan Peock, Margaret Cook, Patricia A. Harrington, Alan Donaldson, Allison M. MaleCarol Anne Gardiner, Helen Gregory, Lucy E. Side, Anne C. Robinson, Louise Emmerson, Ian Ellis, Jean Philippe Peyrat, Joëlle Fournier, Philippe Vennin, Claude Adenis, Danièle Muller, Jean Pierre Fricker, Michel Longy, Olga M. Sinilnikova, Dominique Stoppa-Lyonnet, Rita K. Schmutzler, Beatrix Versmold, Christoph Engel, Alfons Meindl, Karin Kast, Dieter Schaefer, Ursula G. Froster, Georgia Chenevix-Trench, Douglas F. Easton

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

11 Scopus citations

Abstract

Background The transforming growth factor β-1 gene (TGFB1) is a plausible candidate for breast cancer susceptibility. The L10P variant of TGFB1 is associated with higher circulating levels and secretion of TGF-β, and recent large-scale studies suggest strongly that this variant is associated with breast cancer risk in the general population. Methods To evaluate whether TGFB1 L10P also modifies the risk of breast cancer in BRCA1 or BRCA2 mutation carriers, we undertook a multi-center study of 3,442 BRCA1 and 2,095 BRCA2 mutation carriers. Results We found no evidence of association between TGFB1 L10P and breast cancer risk in either BRCA1 or BRCA2 mutation carriers. The per-allele HR for the L10P variant was 1.01 (95%CI: 0.92-1.11) in BRCA1 carriers and 0.92 (95%CI: 0.81-1.04) in BRCA2 mutation carriers. Conclusions These results do not support the hypothesis that TGFB1 L10P genotypes modify the risk of breast cancer in BRCA1 or BRCA2 mutation carriers.

Original language	English (US)
Pages (from-to)	185-192
Number of pages	8
Journal	Breast Cancer Research and Treatment
Volume	115
Issue number	1
DOIs	https://doi.org/10.1007/s10549-008-0064-8
State	Published - May 1 2009

Keywords

BRCA1
BRCA2
Hereditary cancer
Risk modifiers

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1007/s10549-008-0064-8

Cite this

Rebbeck, T. R., Antoniou, A. C., Llopis, T. C., Nevanlinna, H., Aittomäki, K., Simard, J., Spurdle, A. B., Couch, F. J., Pereira, L. H. M., Greene, M. H., Andrulis, I. L., Pasche, B., Kaklamani, V., Hamann, U., Szabo, C., Peock, S., Cook, M., Harrington, P. A., Donaldson, A., ... Easton, D. F. (2009). No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A multi-center cohort study. Breast Cancer Research and Treatment, 115(1), 185-192. https://doi.org/10.1007/s10549-008-0064-8

Rebbeck, TR, Antoniou, AC, Llopis, TC, Nevanlinna, H, Aittomäki, K, Simard, J, Spurdle, AB, Couch, FJ, Pereira, LHM, Greene, MH, Andrulis, IL, Pasche, B, Kaklamani, V, Hamann, U, Szabo, C, Peock, S, Cook, M, Harrington, PA, Donaldson, A, Male, AM, Gardiner, CA, Gregory, H, Side, LE, Robinson, AC, Emmerson, L, Ellis, I, Peyrat, JP, Fournier, J, Vennin, P, Adenis, C, Muller, D, Fricker, JP, Longy, M, Sinilnikova, OM, Stoppa-Lyonnet, D, Schmutzler, RK, Versmold, B, Engel, C, Meindl, A, Kast, K, Schaefer, D, Froster, UG, Chenevix-Trench, G & Easton, DF 2009, 'No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A multi-center cohort study', Breast Cancer Research and Treatment, vol. 115, no. 1, pp. 185-192. https://doi.org/10.1007/s10549-008-0064-8

@article{96da59ed83aa423fa49ce687fa8d364e,

title = "No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A multi-center cohort study",

abstract = "Background The transforming growth factor β-1 gene (TGFB1) is a plausible candidate for breast cancer susceptibility. The L10P variant of TGFB1 is associated with higher circulating levels and secretion of TGF-β, and recent large-scale studies suggest strongly that this variant is associated with breast cancer risk in the general population. Methods To evaluate whether TGFB1 L10P also modifies the risk of breast cancer in BRCA1 or BRCA2 mutation carriers, we undertook a multi-center study of 3,442 BRCA1 and 2,095 BRCA2 mutation carriers. Results We found no evidence of association between TGFB1 L10P and breast cancer risk in either BRCA1 or BRCA2 mutation carriers. The per-allele HR for the L10P variant was 1.01 (95%CI: 0.92-1.11) in BRCA1 carriers and 0.92 (95%CI: 0.81-1.04) in BRCA2 mutation carriers. Conclusions These results do not support the hypothesis that TGFB1 L10P genotypes modify the risk of breast cancer in BRCA1 or BRCA2 mutation carriers.",

keywords = "BRCA1, BRCA2, Hereditary cancer, Risk modifiers",

author = "Rebbeck, {Timothy R.} and Antoniou, {Antonis C.} and Llopis, {Trinidad Caldes} and Heli Nevanlinna and Kristiina Aittom{\"a}ki and Jacques Simard and Spurdle, {Amanda B.} and Couch, {Fergus J.} and Pereira, {Lutecia H.Mateus} and Greene, {Mark H.} and Andrulis, {Irene L.} and Boris Pasche and Virginia Kaklamani and Ute Hamann and Csilla Szabo and Susan Peock and Margaret Cook and Harrington, {Patricia A.} and Alan Donaldson and Male, {Allison M.} and Gardiner, {Carol Anne} and Helen Gregory and Side, {Lucy E.} and Robinson, {Anne C.} and Louise Emmerson and Ian Ellis and Peyrat, {Jean Philippe} and Jo{\"e}lle Fournier and Philippe Vennin and Claude Adenis and Dani{\`e}le Muller and Fricker, {Jean Pierre} and Michel Longy and Sinilnikova, {Olga M.} and Dominique Stoppa-Lyonnet and Schmutzler, {Rita K.} and Beatrix Versmold and Christoph Engel and Alfons Meindl and Karin Kast and Dieter Schaefer and Froster, {Ursula G.} and Georgia Chenevix-Trench and Easton, {Douglas F.}",

note = "Funding Information: German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) GC-HBOC is supported by a grant of the German Cancer Aid (grant107054) and the Center for Molecular Medicine Cologne (grant TV93) to Rita K. Schmutzler. We thank Juliane K{\"o}hler for her excellent technical assistance and the 12 centers of the GC-HBOC for providing samples and clinical data. Helsinki Breast Cancer Study (HEBCS) 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 Tuomas Heikkinen and Kati K{\"a}mpj{\"a}rvi for their contribution in the molecular analyses and Drs. Kirsimari Aaltonen and Carl Blomqvist, for their help in patient sample and data collection. Hospital Clinico San Carlos (HCSC) Trinidad Caldes is funded by FMMA/06 and RTICC06/002/0021 HCSC-Spain. We thank Miguel de la Hoya, Pedro Perez-Segura and Elena Oliveira for their contribution. Funding Information: BCFR was supported by the National Cancer Institute, National Institutes of Health under RFA # CA-95-011 and through cooperative agreements with members of the BCFR, including Cancer Care Ontario (U01 CA69467, PI: Irene A. Andrulis), Columbia University (U01 CA69398, PI: Mary Beth Terry), Fox Chase Cancer Center (U01 CA69631, PI: Mary Daly), Huntsman Cancer Institute (U01 CA69446, PI: Saundra Buys), Northern California Cancer Center (U01 CA69417, PI: Esther M. John), University of Melbourne (U01 CA69638, PI: John L. Hopper), Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute 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 or the CFR. Funding Information: We thank the staff and all of those who participate in the OCGN. We acknowledge the contributions of the provincial familial cancer clinics and molecular diagnostic laboratories and Mona Gill for excellent technical assistance. The OCGN study was supported by funding from Cancer Care Ontario and the National Cancer Institute of Canada with funds from the Terry Fox Run. Deutsches Krebsforschungszentrum study (DKFZ) The DKFZ study was supported by the DKFZ. We thank Diana Torres and Muhammad U. Rashid for providing DNA samples and supplying data. We thank Antje Seidel-Renkert and Michael Gilbert for expert technical assistance. Funding Information: The Kathleen Cunningham Consortium for Research into Familial Breast Cancer (KConFab) We wish to thank Heather Thorne, Eveline Niedermayr, Helene Holland, Xiaoqing Chen and Jonathan Beesley, 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 and 288704) for their contributions to this resource and its management, and the many families who contribute to KConFab. 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. Amanda B. Spurdle and Georgia Chenevix-Trench are NHMRC Career Development Awardee and Senior Principal Research Fellow, respectively. Mayo Clinic Study (MAYO) The Mayo Clinic study was supported by the U.S. Army Medical Research and Materiel Command (W81XWH-04-1-0588), the Mayo Clinic Breast Cancer SPORE (P50-CA116201) and NIH grant CA122340 to Fergus J Couch. We wish to thank Noralane Lindor and Linda Wadum for their contributions. Modifier Study of Quantitative Effects on Disease (Mod-Squad) Csilla I. Szabo is partially supported by a Susan G. Komen Foundation Basic. Clinical and Translational Research Grant (BCTR0402923). Research Project of the Ministry of Education, Youth and Sports of the Czech Republic No MSM0021620808 to Michal Zikan, Zdenek Kleibl and Petr Pohlreich. We acknowledge the contributions of Michal Zikan, Petr Pohlreich and Zdenek Kleibl (Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University Prague, Czech Republic) and Lenka Foretova, Machakova Eva Lukesova Miroslava (Department of Cancer). National Cancer Institute study (NCI) We acknowledge the contributions of Dr. Jeffery Struewing and Marbin A. Pineda from the Laboratory of Population Genetics. Drs. Greene and Struewing were supported by funding from the Intramural Research Program of the US National Cancer Institute. Their data collection efforts were supported by Contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Rockville, MD. Funding Information: Epidemiological study of BRCA1 & BRCA2 mutation carriers (EMBRACE) Margaret Cook, Susan Peock and EMBRACE are funded by Cancer Research–UK. DFE is the PI of the study. EMBRACE Collaborating Centers are: Coordinating Centre, Cambridge: Susan Peock, Margaret Cook, Alexandra Bignell. North of Scotland Regional Genetics Service, Aberdeen: Neva Haites, Helen Gregory. Northern Ireland Regional Genetics Service, Belfast: Patrick Morrison. West Midlands Regional Clinical Genetics Service, Birmingham: Trevor Cole, Carole McKeown. South West Regional Genetics Service, Bristol: Alan Donaldson. East Anglian Regional Genetics Service, Cambridge: Joan Paterson. Medical Genetics Services for Wales, Cardiff: Alexandra Murray, Mark Rogers. St James{\textquoteright}s Hospital, Dublin & National Centre for Medical Genetics, Dublin: Peter Daly, David Barton. South East of Scotland Regional Genetics Service, Edinburgh: Mary Porteous, Michael Steel. Peninsula Clinical Genetics Service. Exeter: Carole Brewer, Julia Rankin. West of Scotland Regional Genetics Service, Glasgow: Rosemarie Davidson, Victoria Murday. South East Thames Regional Genetics Service, Guys Hospital London: Louise Izatt, Gabriella Pichert. North West Thames Regional Genetics Service. Harrow: Huw Dorkins. Leicestershire Clinical Genetics Service, Leicester: Richard Trembath. Yorkshire Regional Genetics Service, Leeds: Tim Bishop, Carol Chu. Merseyside & Cheshire Clinical Genetics Service. Liverpool: Ian Ellis. Manchester Regional Genetics Service, Manchester: D Gareth Evans, Fiona Lalloo, Andrew Shenton. North East Thames Regional Genetics Service, NE Thames: Alison Male, James Mackay, Anne Robinson. Nottingham Clinical Genetics service, Nottingham University Hospitals, Nottingham: Carol Gardiner. Northern Clinical Genetics Service, Newcastle: Fiona Douglas, John Burn. Oxford Regional Genetics Service, Oxford: Lucy Side, Lucy Walker, Sarah Durell. Institute of Cancer Research and Royal Marsden NHS Foundation Trust: Rosalind Eeles. North Trent Clinical Genetics Service, Sheffield: Jackie Cook, Oliver Quarrell. South West Thames Regional Genetics Service, London: Shirley Hodgson. Wessex Clinical Genetics Service. Southampton: Diana Eccles, Anneke Lucassen. Funding Information: Interdisciplinary Health Research International Team Breast Cancer susceptibility (INHERIT) Jacques Simard, Francine Durocher, Rachel Laframboise, Marie Plante, Centre Hospitalier Universitaire de Qu{\'e}bec & Laval University, Qu{\'e}bec, Canada; Peter Bridge, Jilian Parboosingh, Molecular Diagnostic Laboratory, Alberta Children{\textquoteright}s Hospital, Calgary, Canada; Jocelyne Chiquette, H{\^o}pital du Saint-Sacrement, Qu{\'e}bec, Canada; Bernard Lesperance, Roxanne Pichette, H{\^o}pital du Sacr{\'e}-C{\oe}ur de Montr{\'e}al, Montr{\'e}al, Canada. This work was supported by the Canadian Institutes of Health Research for the INHERIT BRCAs program, the CURE Foundation and the Fonds de la recherche en Sant{\'e} du Quebec/Reseau de Medecine Genetique Appliquee. Funding Information: Genetic Modifiers of cancer risk in BRCA1/2 mutation carriers study (GEMO) We wish to thank Laure Barjhoux for management the GEMO samples and carrying out genotyping, and all the GEMO centers for their contributions to this resource. The GEMO study was supported by the Programme Hospitalier de Recherche Clinique AOR01082, by Programme Incitatif et Coop{\'e}ratif G{\'e}n{\'e}tique et Biologie de Cancer du Sein, Institut Curie, and by the Association {\textquoteleft}{\textquoteleft}Le cancer du sein, parlons-en!{\textquoteright}{\textquoteright} Award.",

year = "2009",

month = may,

day = "1",

doi = "10.1007/s10549-008-0064-8",

language = "English (US)",

volume = "115",

pages = "185--192",

journal = "Breast Cancer Research and Treatment",

issn = "0167-6806",

publisher = "Springer New York",

number = "1",

}

TY - JOUR

T1 - No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers

T2 - A multi-center cohort study

AU - Rebbeck, Timothy R.

AU - Antoniou, Antonis C.

AU - Llopis, Trinidad Caldes

AU - Nevanlinna, Heli

AU - Aittomäki, Kristiina

AU - Simard, Jacques

AU - Spurdle, Amanda B.

AU - Couch, Fergus J.

AU - Pereira, Lutecia H.Mateus

AU - Greene, Mark H.

AU - Andrulis, Irene L.

AU - Pasche, Boris

AU - Kaklamani, Virginia

AU - Hamann, Ute

AU - Szabo, Csilla

AU - Peock, Susan

AU - Cook, Margaret

AU - Harrington, Patricia A.

AU - Donaldson, Alan

AU - Male, Allison M.

AU - Gardiner, Carol Anne

AU - Gregory, Helen

AU - Side, Lucy E.

AU - Robinson, Anne C.

AU - Emmerson, Louise

AU - Ellis, Ian

AU - Peyrat, Jean Philippe

AU - Fournier, Joëlle

AU - Vennin, Philippe

AU - Adenis, Claude

AU - Muller, Danièle

AU - Fricker, Jean Pierre

AU - Longy, Michel

AU - Sinilnikova, Olga M.

AU - Stoppa-Lyonnet, Dominique

AU - Schmutzler, Rita K.

AU - Versmold, Beatrix

AU - Engel, Christoph

AU - Meindl, Alfons

AU - Kast, Karin

AU - Schaefer, Dieter

AU - Froster, Ursula G.

AU - Chenevix-Trench, Georgia

AU - Easton, Douglas F.

N1 - Funding Information: German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) GC-HBOC is supported by a grant of the German Cancer Aid (grant107054) and the Center for Molecular Medicine Cologne (grant TV93) to Rita K. Schmutzler. We thank Juliane Köhler for her excellent technical assistance and the 12 centers of the GC-HBOC for providing samples and clinical data. Helsinki Breast Cancer Study (HEBCS) 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 Tuomas Heikkinen and Kati Kämpjärvi for their contribution in the molecular analyses and Drs. Kirsimari Aaltonen and Carl Blomqvist, for their help in patient sample and data collection. Hospital Clinico San Carlos (HCSC) Trinidad Caldes is funded by FMMA/06 and RTICC06/002/0021 HCSC-Spain. We thank Miguel de la Hoya, Pedro Perez-Segura and Elena Oliveira for their contribution. Funding Information: BCFR was supported by the National Cancer Institute, National Institutes of Health under RFA # CA-95-011 and through cooperative agreements with members of the BCFR, including Cancer Care Ontario (U01 CA69467, PI: Irene A. Andrulis), Columbia University (U01 CA69398, PI: Mary Beth Terry), Fox Chase Cancer Center (U01 CA69631, PI: Mary Daly), Huntsman Cancer Institute (U01 CA69446, PI: Saundra Buys), Northern California Cancer Center (U01 CA69417, PI: Esther M. John), University of Melbourne (U01 CA69638, PI: John L. Hopper), Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute 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 or the CFR. Funding Information: We thank the staff and all of those who participate in the OCGN. We acknowledge the contributions of the provincial familial cancer clinics and molecular diagnostic laboratories and Mona Gill for excellent technical assistance. The OCGN study was supported by funding from Cancer Care Ontario and the National Cancer Institute of Canada with funds from the Terry Fox Run. Deutsches Krebsforschungszentrum study (DKFZ) The DKFZ study was supported by the DKFZ. We thank Diana Torres and Muhammad U. Rashid for providing DNA samples and supplying data. We thank Antje Seidel-Renkert and Michael Gilbert for expert technical assistance. Funding Information: The Kathleen Cunningham Consortium for Research into Familial Breast Cancer (KConFab) We wish to thank Heather Thorne, Eveline Niedermayr, Helene Holland, Xiaoqing Chen and Jonathan Beesley, 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 and 288704) for their contributions to this resource and its management, and the many families who contribute to KConFab. 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. Amanda B. Spurdle and Georgia Chenevix-Trench are NHMRC Career Development Awardee and Senior Principal Research Fellow, respectively. Mayo Clinic Study (MAYO) The Mayo Clinic study was supported by the U.S. Army Medical Research and Materiel Command (W81XWH-04-1-0588), the Mayo Clinic Breast Cancer SPORE (P50-CA116201) and NIH grant CA122340 to Fergus J Couch. We wish to thank Noralane Lindor and Linda Wadum for their contributions. Modifier Study of Quantitative Effects on Disease (Mod-Squad) Csilla I. Szabo is partially supported by a Susan G. Komen Foundation Basic. Clinical and Translational Research Grant (BCTR0402923). Research Project of the Ministry of Education, Youth and Sports of the Czech Republic No MSM0021620808 to Michal Zikan, Zdenek Kleibl and Petr Pohlreich. We acknowledge the contributions of Michal Zikan, Petr Pohlreich and Zdenek Kleibl (Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University Prague, Czech Republic) and Lenka Foretova, Machakova Eva Lukesova Miroslava (Department of Cancer). National Cancer Institute study (NCI) We acknowledge the contributions of Dr. Jeffery Struewing and Marbin A. Pineda from the Laboratory of Population Genetics. Drs. Greene and Struewing were supported by funding from the Intramural Research Program of the US National Cancer Institute. Their data collection efforts were supported by Contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Rockville, MD. Funding Information: Epidemiological study of BRCA1 & BRCA2 mutation carriers (EMBRACE) Margaret Cook, Susan Peock and EMBRACE are funded by Cancer Research–UK. DFE is the PI of the study. EMBRACE Collaborating Centers are: Coordinating Centre, Cambridge: Susan Peock, Margaret Cook, Alexandra Bignell. North of Scotland Regional Genetics Service, Aberdeen: Neva Haites, Helen Gregory. Northern Ireland Regional Genetics Service, Belfast: Patrick Morrison. West Midlands Regional Clinical Genetics Service, Birmingham: Trevor Cole, Carole McKeown. South West Regional Genetics Service, Bristol: Alan Donaldson. East Anglian Regional Genetics Service, Cambridge: Joan Paterson. Medical Genetics Services for Wales, Cardiff: Alexandra Murray, Mark Rogers. St James’s Hospital, Dublin & National Centre for Medical Genetics, Dublin: Peter Daly, David Barton. South East of Scotland Regional Genetics Service, Edinburgh: Mary Porteous, Michael Steel. Peninsula Clinical Genetics Service. Exeter: Carole Brewer, Julia Rankin. West of Scotland Regional Genetics Service, Glasgow: Rosemarie Davidson, Victoria Murday. South East Thames Regional Genetics Service, Guys Hospital London: Louise Izatt, Gabriella Pichert. North West Thames Regional Genetics Service. Harrow: Huw Dorkins. Leicestershire Clinical Genetics Service, Leicester: Richard Trembath. Yorkshire Regional Genetics Service, Leeds: Tim Bishop, Carol Chu. Merseyside & Cheshire Clinical Genetics Service. Liverpool: Ian Ellis. Manchester Regional Genetics Service, Manchester: D Gareth Evans, Fiona Lalloo, Andrew Shenton. North East Thames Regional Genetics Service, NE Thames: Alison Male, James Mackay, Anne Robinson. Nottingham Clinical Genetics service, Nottingham University Hospitals, Nottingham: Carol Gardiner. Northern Clinical Genetics Service, Newcastle: Fiona Douglas, John Burn. Oxford Regional Genetics Service, Oxford: Lucy Side, Lucy Walker, Sarah Durell. Institute of Cancer Research and Royal Marsden NHS Foundation Trust: Rosalind Eeles. North Trent Clinical Genetics Service, Sheffield: Jackie Cook, Oliver Quarrell. South West Thames Regional Genetics Service, London: Shirley Hodgson. Wessex Clinical Genetics Service. Southampton: Diana Eccles, Anneke Lucassen. Funding Information: Interdisciplinary Health Research International Team Breast Cancer susceptibility (INHERIT) Jacques Simard, Francine Durocher, Rachel Laframboise, Marie Plante, Centre Hospitalier Universitaire de Québec & Laval University, Québec, Canada; Peter Bridge, Jilian Parboosingh, Molecular Diagnostic Laboratory, Alberta Children’s Hospital, Calgary, Canada; Jocelyne Chiquette, Hôpital du Saint-Sacrement, Québec, Canada; Bernard Lesperance, Roxanne Pichette, Hôpital du Sacré-Cœur de Montréal, Montréal, Canada. This work was supported by the Canadian Institutes of Health Research for the INHERIT BRCAs program, the CURE Foundation and the Fonds de la recherche en Santé du Quebec/Reseau de Medecine Genetique Appliquee. Funding Information: Genetic Modifiers of cancer risk in BRCA1/2 mutation carriers study (GEMO) We wish to thank Laure Barjhoux for management the GEMO samples and carrying out genotyping, and all the GEMO centers for their contributions to this resource. The GEMO study was supported by the Programme Hospitalier de Recherche Clinique AOR01082, by Programme Incitatif et Coopératif Génétique et Biologie de Cancer du Sein, Institut Curie, and by the Association ‘‘Le cancer du sein, parlons-en!’’ Award.

PY - 2009/5/1

Y1 - 2009/5/1

N2 - Background The transforming growth factor β-1 gene (TGFB1) is a plausible candidate for breast cancer susceptibility. The L10P variant of TGFB1 is associated with higher circulating levels and secretion of TGF-β, and recent large-scale studies suggest strongly that this variant is associated with breast cancer risk in the general population. Methods To evaluate whether TGFB1 L10P also modifies the risk of breast cancer in BRCA1 or BRCA2 mutation carriers, we undertook a multi-center study of 3,442 BRCA1 and 2,095 BRCA2 mutation carriers. Results We found no evidence of association between TGFB1 L10P and breast cancer risk in either BRCA1 or BRCA2 mutation carriers. The per-allele HR for the L10P variant was 1.01 (95%CI: 0.92-1.11) in BRCA1 carriers and 0.92 (95%CI: 0.81-1.04) in BRCA2 mutation carriers. Conclusions These results do not support the hypothesis that TGFB1 L10P genotypes modify the risk of breast cancer in BRCA1 or BRCA2 mutation carriers.

AB - Background The transforming growth factor β-1 gene (TGFB1) is a plausible candidate for breast cancer susceptibility. The L10P variant of TGFB1 is associated with higher circulating levels and secretion of TGF-β, and recent large-scale studies suggest strongly that this variant is associated with breast cancer risk in the general population. Methods To evaluate whether TGFB1 L10P also modifies the risk of breast cancer in BRCA1 or BRCA2 mutation carriers, we undertook a multi-center study of 3,442 BRCA1 and 2,095 BRCA2 mutation carriers. Results We found no evidence of association between TGFB1 L10P and breast cancer risk in either BRCA1 or BRCA2 mutation carriers. The per-allele HR for the L10P variant was 1.01 (95%CI: 0.92-1.11) in BRCA1 carriers and 0.92 (95%CI: 0.81-1.04) in BRCA2 mutation carriers. Conclusions These results do not support the hypothesis that TGFB1 L10P genotypes modify the risk of breast cancer in BRCA1 or BRCA2 mutation carriers.

KW - BRCA1

KW - BRCA2

KW - Hereditary cancer

KW - Risk modifiers

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U2 - 10.1007/s10549-008-0064-8

DO - 10.1007/s10549-008-0064-8

M3 - Article

C2 - 18523885

AN - SCOPUS:67349158309

SN - 0167-6806

VL - 115

SP - 185

EP - 192

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

IS - 1

ER -

No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A multi-center cohort study

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