Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1/2 carrier cohort (GENEPSO). - Archive ouverte HAL Access content directly
Journal Articles Breast Cancer Research Year : 2012

Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1/2 carrier cohort (GENEPSO).

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Catherine Noguès
  • Function : Author
  • PersonId : 928987
Emmanuelle Mouret-Fourme
  • Function : Author
  • PersonId : 928988
Marion Gauthier-Villars
  • Function : Author
  • PersonId : 907333
Jean-Pierre Fricker
  • Function : Author
  • PersonId : 910039
Olivier Caron
  • Function : Author
  • PersonId : 856301
Pascaline Berthet
  • Function : Author
  • PersonId : 920652
Bruno Buecher
  • Function : Author
  • PersonId : 907332
Laurence Gladieff
  • Function : Author
  • PersonId : 898524
Paul Gesta
  • Function : Author
  • PersonId : 912528
Marc Frénay
  • Function : Author
  • PersonId : 912527
Alain Lortholary
  • Function : Author
  • PersonId : 928991
Michel Longy
  • Function : Author
  • PersonId : 918895
Pascal Pujol
  • Function : Author
  • PersonId : 840596
Julie Tinat
  • Function : Author
  • PersonId : 928994
Rosette Lidereau
  • Function : Author
  • PersonId : 918694

Abstract

ABSTRACT: INTRODUCTION: Mutations in BRCA1 and BRCA2 confer a high risk of breast cancer (BC), but the magnitude of this risk seems to vary according to the study and various factors. Although controversial, there are data to support the hypothesis of allelic risk heterogeneity. METHODS: We assessed variation in BC risk according to factors related to pregnancies by location of mutation in homogeneous risk region of BRCA1 and BRCA2 in 990 women of the French study GENEPSO by using a weighted Cox regression model. RESULTS: Our results confirm the existence of a protective effect of an increasing number of full-term pregnancies (FTPs) toward BC among BRCA1 and BRCA2 mutation carriers ([greater than or equal to]3 vs. 0 FTPs: HR=0.51, 95% CI=0.33-0.81). Additionally, hazard ratio (HR) show an association between incomplete pregnancies and a higher BC risk, which reached 2.39 (95% CI=1.28-4.45) among women who had at least three incomplete pregnancies when compared with women with zero incomplete pregnancies. This increased risk appeared to be restricted to incomplete pregnancies occurring before the first FTP (HR=1.77, 95% CI=1.19-2.63). We defined the TMAP score (defined as the Time of breast Mitotic Activity during Pregnancies) to take into account simultaneously the opposite effect of full-term and interrupted pregnancies. Compared with women with a TMAP score of less than 0.35, an increasing TMAP score was associated with a statistically significant increase in the risk of BC (P trend=0.02) which reached 1.97 (95% CI=1.19-3.29) for a TMAP score > 0.5 (vs. TMAP less than or equal to 0.35). All these results appeared to be similar in BRCA1 and BRCA2. Nevertheless, our results suggest a variation in BC risk associated with parity according to the location of the mutation in BRCA1. Indeed, parity seems to be associated with a significantly decreased risk of BC only among women with a mutation in the central region of BRCA1 (low-risk region) (greater than or equal to 1 vs. 0 FTP: HR=0.27, 95% CI=0.13-0.55) (pinteraction <10-3). CONCLUSION: Our findings show that, taking into account environmental and lifestyle modifiers, mutation position might be important for the clinical management of BRCA1 and BRCA2 mutation carriers and could also be helpful in understanding how BRCA1 and BRCA2 genes are involved in BC.
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Dates and versions

inserm-00724092 , version 1 (17-08-2012)

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Cite

Julie Lecarpentier, Catherine Noguès, Emmanuelle Mouret-Fourme, Marion Gauthier-Villars, Christine Lasset, et al.. Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1/2 carrier cohort (GENEPSO).. Breast Cancer Research, 2012, 14 (4), pp.R99. ⟨10.1186/bcr3218⟩. ⟨inserm-00724092⟩
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