Variation in breast cancer risk with mutation position smoking alcohol and chest X-ray history in the French National BRCA1/2 carrier cohort (GENEPSO) - Centre Paul Strauss Access content directly
Journal Articles Breast Cancer Research and Treatment Year : 2011

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

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.
Fichier principal
Vignette du fichier
Lecarpentier2011.pdf (154.08 Ko) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-00698006 , version 1 (26-08-2022)

Licence

Attribution - NonCommercial

Identifiers

Cite

Julie Lecarpentier, Catherine Noguès, Emmanuelle Mouret-Fourme, Dominique Stoppa-Lyonnet, Christine Lasset, et al.. Variation in breast cancer risk with mutation position smoking alcohol and chest X-ray history in the French National BRCA1/2 carrier cohort (GENEPSO). Breast Cancer Research and Treatment, 2011, 130 (3), pp.927-938. ⟨10.1007/s10549-011-1655-3⟩. ⟨hal-00698006⟩
287 View
112 Download

Altmetric

Share

Gmail Facebook X LinkedIn More