Breast Cancer Research and Treatment

, Volume 130, Issue 3, pp 927–938

Variation in breast cancer risk with mutation position, smoking, alcohol, and chest X-ray history, in the French National BRCA1/2 carrier cohort (GENEPSO)

  • Julie Lecarpentier
  • Catherine Noguès
  • Emmanuelle Mouret-Fourme
  • Dominique Stoppa-Lyonnet
  • Christine Lasset
  • Olivier Caron
  • Jean-Pierre Fricker
  • Laurence Gladieff
  • Laurence Faivre
  • Hagay Sobol
  • Paul Gesta
  • Marc Frenay
  • Elisabeth Luporsi
  • Isabelle Coupier
  • GENEPSO
  • Rosette Lidereau
  • Nadine Andrieu
Epidemiology

DOI: 10.1007/s10549-011-1655-3

Cite this article as:
Lecarpentier, J., Noguès, C., Mouret-Fourme, E. et al. Breast Cancer Res Treat (2011) 130: 927. doi:10.1007/s10549-011-1655-3

Abstract

Germline mutations in BRCA1/2 confer a high risk of breast cancer (BC), but the magnitude of this risk varies according to various factors. Although controversial, there are data to support the hypothesis of allelic-risk heterogeneity. We assessed variation in BC risk according to the location of mutations recorded in the French study GENEPSO. Since the women in this study were selected from high-risk families, oversampling of affected women was eliminated by using a weighted Cox-regression model. Women were censored at the date of diagnosis when affected by any cancer, or the date of interview when unaffected. A total of 990 women were selected for the analysis: 379 were classified as affected, 611 as unaffected. For BRCA1, there was some evidence of a central region where the risk of BC is lower (codons 374–1161) (HR = 0.59, P = 0.04). For BRCA2, there was a strong evidence for a region at decreased risk (codons 957–1827) (HR = 0.35, P = 0.005) and for one at increased risk (codons 2546–2968) (HR = 3.56, P = 0.01). Moreover, we found an important association between radiation exposure from chest X-rays and BC risk (HR = 4.29, P < 10−3) and a positive association between smoking more than 21 pack-years and BC risk (HR = 2.09, P = 0.04). No significant variation in BC risk associated with chest X-ray exposure, smoking, and alcohol consumption was found according to the location of the mutation in BRCA1 and BRCA2. Our findings are consistent with those suggesting that the risk of BC is lower in the central regions of BRCA1/2. A new high-risk region in BRCA2 is described. Taking into account environmental and lifestyle modifiers, the location of mutations might be important in the clinical management of BRCA mutation carriers.

Keywords

Breast cancerRisk factorGenotype–phenotype correlationBRCA1BRCA2Interaction

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Julie Lecarpentier
    • 1
    • 2
    • 3
  • Catherine Noguès
    • 4
  • Emmanuelle Mouret-Fourme
    • 4
  • Dominique Stoppa-Lyonnet
    • 5
  • Christine Lasset
    • 6
  • Olivier Caron
    • 7
  • Jean-Pierre Fricker
    • 8
  • Laurence Gladieff
    • 9
  • Laurence Faivre
    • 10
  • Hagay Sobol
    • 11
  • Paul Gesta
    • 12
  • Marc Frenay
    • 13
  • Elisabeth Luporsi
    • 14
  • Isabelle Coupier
    • 15
  • GENEPSO
  • Rosette Lidereau
    • 16
  • Nadine Andrieu
    • 1
    • 2
    • 3
  1. 1.Institut National de la Santé et de la Recherche MédicaleParis Cedex 05France
  2. 2.Institut CurieCentre de Recherche – Service de BiostatistiquesParis Cedex 05France
  3. 3.Ecole des Mines de ParisParis TechFontainebleauFrance
  4. 4.Institut CurieHôpital René HugueninSaint-CloudFrance
  5. 5.Institut National de la Santé et de la Recherche Médicale, Unité U509, Service de Génétique Oncologique, Institut CurieUniversité Paris-DescartesParisFrance
  6. 6.Centre Léon BérardDépartement de Santé PubliqueLyonFrance
  7. 7.Institut de Cancérologie Gustave Roussy, Service d’Oncologie GénétiqueVillejuifFrance
  8. 8.Centre Paul StraussUnité d’OncologieStrasbourgFrance
  9. 9.Institut Claudius RegaudService d’Oncologie MédicaleToulouseFrance
  10. 10.Centre Georges Francois Leclerc, Oncogénétique and Hôpital d’EnfantsService de Génétique MédicaleDijonFrance
  11. 11.Institut Paoli-CalmettesDépartement d’Oncologie GénétiqueMarseilleFrance
  12. 12.C.H.R. Georges RenonPôle OncologieNiortFrance
  13. 13.Centre Antoine Lacassagne, Unité d’OncogénétiqueNiceFrance
  14. 14.Centre Alexis VautrinVandoeuvre-les-NancyFrance
  15. 15.Hopital Arnaud de Villeneuve, CHU Montpellier, Service de Génétique médicale et OncogénétiqueMontpellierFrance
  16. 16.Institut National de la Santé et de la Recherche Médicale, Unité U735 and Laboratoire d’OncogénétiqueHôpital René HugueninSaint-CloudFrance