Risk factors for ovarian cancer by BRCA status: a collaborative case-only analysis
Menée à l'aide des données de cinq études de l'"Ovarian Cancer Association Consortium" incluant 4 926 patientes atteintes d'un cancer de l'ovaire, cette étude analyse l'influence de facteurs reproductifs, hormonaux ou comportementaux sur le risque de développer la maladie, en fonction du statut mutationnel de BRCA
Background: Women with an inherited pathogenic variant in BRCA1 or BRCA2 have a greatly increased risk of developing ovarian cancer, but the importance of behavioral factors is less clear. We used a case-only design to compare the magnitude of associations with established reproductive, hormonal and lifestyle risk factors between BRCA mutation carriers and non-carriers. Methods: We pooled data from five studies from the Ovarian Cancer Association Consortium including 637 BRCA carriers and 4289 non-carriers. Covariate-adjusted generalized linear mixed models were used to estimate interaction risk ratios (IRRs) and 95% confidence intervals, with BRCA (carrier vs. non-carrier) as the response variable. Results: IRRs were above 1.0 for known protective factors including ever being pregnant (IRR=1.29, 95%CI 1.00-1.67) and ever using the oral contraceptive pill (1.30, 95%CI 1.07-1.60), suggesting the protective effects of these factors may be reduced in carriers compared with non-carriers. Conversely, the IRRs for risk factors including endometriosis and menopausal hormone therapy were below 1.0, suggesting weaker positive associations among BRCA carriers. In contrast, associations with lifestyle factors including smoking, physical inactivity, BMI and aspirin use did not appear to differ by BRCA status. Conclusions: Our results suggest that associations with hormonal and reproductive factors are generally weaker for those with a pathogenic BRCA variant than those without, while associations with modifiable lifestyle factors are similar for carriers and non-carriers. Impact Advice to maintain a healthy weight, be physically active and refrain from smoking will therefore benefit BRCA carriers as well as non-carriers.