Reproductive windows, genetic loci and breast cancer risk
A partir des données de l'étude "Collaborative Breast Cancer Study" portant sur 6 131 cas et 7 274 témoins, cette étude évalue l'association entre des critères reproductifs (délai entre les premières règles et la première naissance, délai entre les premières règles et la ménopause), 13 variants génétiques déjà identifiés dans des études d'association sur le génome entier et le risque de cancer du sein
Purpose : The reproductive windows between age at menarche and first childbirth (standardized AFB) and from menarche to menopause (reproductive lifespan) may interact with genetic variants in association with breast cancer risk. Methods : We assessed this hypothesis in 6131 breast cancer cases and 7274 controls who participated in the population-based Collaborative Breast Cancer Study. Risk factor information was collected through telephone interviews and DNA samples were collected on a sub-sample (N=1484 cases, 1307 controls) to genotype for 13 genome-wide association study-identified loci. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated and P-values for the interaction between reproductive windows and genotypes were obtained by adding cross-product terms to statistical models. Results : For standardized AFB, the OR was 1.52 (CI:1.36-1.71) comparing the highest to lowest quintile. Carrier status for rs10941679 (5p12) and rs10483813 (RAD51B) appeared to modify this relationship (P=0.04 and P=0.02, respectively). For reproductive lifespan, the OR comparing the highest and lowest quintiles was 1.62 (CI:1.35-1.95). No interactions were detected between genotype and reproductive lifespan (all P>0.05). All results were similar regardless of ductal versus lobular breast cancer subtype. Conclusions : Our results suggest reproductive windows are associated with breast cancer risk, and that associations may vary by genetic variants.