Breast cancer risk associated with oestrogen exposure and truncating mutation location in BRCA1/2 carriers.
Fiche publication
Date publication
janvier 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LUPORSI Elisabeth, Dr MAUGARD Christine
Tous les auteurs :
Lecarpentier J, Nogues C, Mouret-Fourme E, Buecher B, Gauthier-Villars M, Stoppa-Lyonnet D, Bonadona V, Fricker JP, Berthet P, Caron O, Coupier I, Pujol P, Faivre L, Gesta P, Eisinger F, Mari V, Gladieff L, Lortholary A, Luporsi E, Leroux D, Venat-Bouvet L, Maugard CM, Colas C, Tinat J, Lasset C, Andrieu N
Lien Pubmed
Résumé
Background: Mutations in BRCA1/2 confer a high risk of breast cancer (BC), but literature values of this risk vary. A genotype-phenotype correlation has been found in both genes and the effect of reproductive factors differs according to mutation location. We hypothesize that such a variation may exist for other factors related to estrogen exposure. Methods: We used a weighted Cox regression model to assess variation in BC risk with these factors using location of mutation in homogeneous BC risk region of BRCA1/2 in the GENEPSO study. Results: We found that late age at menarche reduced BC risk by 31% and that among BRCA1 carriers, a long or a short menstrual cycle increased risk (by 35% and 48%, respectively). Among premenopausal women, overweight was associated with a 39% decrease in BC risk while underweight was associated with an increased risk (hazard ratio [HR]=2.09). A natural menopause, mainly after age 50, was associated with a high BC risk (HR=2.46) and a significant interaction between menopause status and the location of mutations was found leading up to 10% variation in absolute risk according to the age at menopause. Conclusions: As observed in the general population, late menarche, long or short menstrual cycle, over- or under-weight, and being post-menopausal were associated with BC risk in BRCA1/2 carriers. The association with the menopause was observed only when the mutation was located in the "high-risk" zones. Impact: Taking into account modifier factors, location of mutation might be important for the clinical management of BRCA1/2 carriers.
Référence
Cancer Epidemiol Biomarkers Prev. 2015 Jan 22. pii: cebp.0884.2014.