Breast Cancer Research and Treatment

, Volume 115, Issue 1, pp 185–192

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
  • KConFab
  • Fergus J. Couch
  • Lutecia H. Mateus Pereira
  • Mark H. Greene
  • Irene L. Andrulis
  • Ontario Cancer Genetics Network
  • Boris Pasche
  • Virginia Kaklamani
  • Breast Cancer Family Registry
  • 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
  • EMBRACE
  • Jean-Philippe Peyrat
  • Joëlle Fournier
  • Philippe Vennin
  • Claude Adenis
  • Danièle Muller
  • Jean-Pierre Fricker
  • Michel Longy
  • Olga M. Sinilnikova
  • Dominique Stoppa-Lyonnet
  • GEMO
  • Rita K. Schmutzler
  • Beatrix Versmold
  • Christoph Engel
  • Alfons Meindl
  • Karin Kast
  • Dieter Schaefer
  • Ursula G. Froster
  • Georgia Chenevix-Trench
  • Douglas F. Easton
Epidemiology

DOI: 10.1007/s10549-008-0064-8

Cite this article as:
Rebbeck, T.R., Antoniou, A.C., Llopis, T.C. et al. Breast Cancer Res Treat (2009) 115: 185. doi:10.1007/s10549-008-0064-8

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

BRCA1BRCA2Risk modifiersHereditary cancer

Abbreviations

CIMBA

Consortium of Investigators of Modifiers of BRCA1/2

BCAC

Breast Cancer Association Consortium

BCFR

Breast Cancer Family Registries

DKFZ

Deutsche Krebsforschungszentrum

EMBRACE

Epidemiological Study of Familial Breast Cancer

GC-HBOC

German Consortium of Hereditary Breast and Ovarian Cancer

HEBCS

Helsinki Breast Cancer Study

HCSC

Hospital Clinico San Carlos

HR

Hazard ratio

INHERIT

Interdisciplinary Health Research International Team Breast Cancer Susceptibility

KConFab

The Kathleen Cunningham Consortium for Research into Familial Breast Cancer

MOD-Squad

Modifier study of quantitative effects on disease

NCI

National Cancer Institute Study

OCGN

Ontario Cancer Genetics Network Study

GEMO

Genetic Modifiers of cancer risk in BRCA1/2 mutation carriers study

TGF-β

Transforming growth factor-β

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Timothy R. Rebbeck
    • 1
  • Antonis C. Antoniou
    • 2
  • Trinidad Caldes Llopis
    • 3
  • Heli Nevanlinna
    • 4
  • Kristiina Aittomäki
    • 5
  • Jacques Simard
    • 6
  • Amanda B. Spurdle
    • 7
  • KConFab
    • 8
  • Fergus J. Couch
    • 9
  • Lutecia H. Mateus Pereira
    • 10
    • 11
  • Mark H. Greene
    • 12
  • Irene L. Andrulis
    • 13
    • 14
  • Ontario Cancer Genetics Network
    • 15
  • Boris Pasche
    • 16
  • Virginia Kaklamani
    • 16
  • Breast Cancer Family Registry
    • 17
  • Ute Hamann
    • 18
  • Csilla Szabo
    • 9
  • Susan Peock
    • 2
  • Margaret Cook
    • 2
  • Patricia A. Harrington
    • 19
  • Alan Donaldson
    • 20
  • Allison M. Male
    • 21
  • Carol Anne Gardiner
    • 22
  • Helen Gregory
    • 23
  • Lucy E. Side
    • 24
  • Anne C. Robinson
    • 25
  • Louise Emmerson
    • 26
  • Ian Ellis
    • 27
  • EMBRACE
    • 2
  • Jean-Philippe Peyrat
    • 28
  • Joëlle Fournier
    • 28
  • Philippe Vennin
    • 28
  • Claude Adenis
    • 28
  • Danièle Muller
    • 29
  • Jean-Pierre Fricker
    • 29
  • Michel Longy
    • 30
  • Olga M. Sinilnikova
    • 31
    • 32
  • Dominique Stoppa-Lyonnet
    • 33
  • GEMO
    • 31
  • Rita K. Schmutzler
    • 34
  • Beatrix Versmold
    • 34
  • Christoph Engel
    • 35
  • Alfons Meindl
    • 36
  • Karin Kast
    • 37
  • Dieter Schaefer
    • 38
  • Ursula G. Froster
    • 39
  • Georgia Chenevix-Trench
    • 7
  • Douglas F. Easton
    • 2
  1. 1.Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and BiostatisticsUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  2. 2.Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK
  3. 3.Medical Oncology BranchHospital Clinico San Carlos (HCSC)MadridSpain
  4. 4.Department of Obstetrics and GynecologyHelsinki University Central HospitalHelsinkiFinland
  5. 5.Department of Clinical GeneticsHelsinki University Central HospitalHelsinkiFinland
  6. 6.Cancer Genomics Laboratory, Oncology and Molecular Endocrinology Research CenterCentre Hospitalier Universitaire de Quebec and Université LavalQuebec CityCanada
  7. 7.Queensland Institute of Medical ResearchBrisbaneAustralia
  8. 8.Peter MacCallum Cancer CentreMelbourneAustralia
  9. 9.Department of Laboratory Medicine and PathologyMayo Clinic College of MedicineRochesterUSA
  10. 10.Laboratory of Population GeneticsCenter for Cancer Research, National Cancer InstituteBethesdaUSA
  11. 11.University of Miami Sylvester Comprehensive Cancer CenterMiamiUSA
  12. 12.Clinical Genetics Branch, Division of Cancer Epidemiology and GeneticsNCIRockvilleUSA
  13. 13.Fred A. Litwin Center for Cancer Genetics, Samuel Lunenfeld Research InstituteMount Sinai HospitalTorontoCanada
  14. 14.Cancer Care OntarioTorontoCanada
  15. 15.Ontario Cancer Genetics NetworkTorontoCanada
  16. 16.Division Hematology/Oncology, Robert H. Lurie Comprehensive Cancer CenterNorthwestern University Feinberg School of MedicineChicago USA
  17. 17.Breast Cancer Family RegistryToronto Canada
  18. 18.Deutsches Krebsforschungszentrum (DKFZ)HeidelbergGermany
  19. 19.Cancer Research UK Department of OncologyUniversity of CambridgeCambridgeUK
  20. 20.South Western Regional Genetics ServiceSt Michael’s HospitalBristolUK
  21. 21.Clinical and Molecular Genetics UnitInstitute of Child Health and Great Ormond Street HospitalLondonUK
  22. 22.Nottingham Centre for Medical GeneticsNottingham University Hospitals NHS TrustNottinghamUK
  23. 23.North of Scotland Regional Genetics ServiceNHS Grampian & University of AberdeenAberdeenUK
  24. 24.Oxford Regional Genetics ServiceChurchill HospitalOxfordUK
  25. 25.South Essex Cancer Research NetworkSouthend University Hospital NHS Foundation TrustSouthendUK
  26. 26.All Wales Medical Genetics ServiceGlan Clwyd HospitalRhylUK
  27. 27.Department of Clinical GeneticsAlder Hey Children’s HospitalLiverpoolUK
  28. 28.Centre Oscar LambretLilleFrance
  29. 29.Centre Paul StraussStrasbourgFrance
  30. 30.Institut BergoniéBordeauxFrance
  31. 31.Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon/Centre Léon BérardUMR5201 CNRS-Université Claude BernardLyonFrance
  32. 32.Laboratoire de Génétique MoléculaireUMR5201 CNRS-Université Claude BernardLyonFrance
  33. 33.INSERM U509, Service de Génétique OncologiqueInstitut CurieParisFrance
  34. 34.Division of Molecular Gyneco-Oncology, Department for Obstetrics and GynecologyUniversity of CologneCologneGermany
  35. 35.Institute for Medical Informatics, Statistics and EpidemiologyUniversity of LeipzigLeipzigGermany
  36. 36.Department of Gynaecology and ObstetricsTechnical UniversityMunichGermany
  37. 37.Department of Gynaecology and ObstetricsTechnical UniversityDresdenGermany
  38. 38.Institute of Human GeneticsUniversity of FrankfurtFrankfurtGermany
  39. 39.Institute of Human GeneticsUniversity of LeipzigLeipzigGermany