Risk Factors for Ovarian Cancer by BRCA Status: A Collaborative Case-Only Analysis

Gersekowski, K; Na, R; Alsop, K; Delahunty, R; Goode, EL; Cunningham, JM; Winham, SJ; Pharoah, PDP; Song, H; Webb, PM

Author(s): Gersekowski, K; Na, R; Alsop, K; Delahunty, R; Goode, EL; Cunningham, JM; Winham, SJ; Pharoah, PDP; Song, H; Webb, PM;
Details: Publication Year 2024-04-03,Volume 33,Issue #4,Page 586-592
Journal Title: Cancer Epidemiology, Biomarkers & Prevention
Publication Type: Research article
Abstract: 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 noncarriers. METHODS: We pooled data from five studies from the Ovarian Cancer Association Consortium including 637 BRCA carriers and 4,289 noncarriers. Covariate-adjusted generalized linear mixed models were used to estimate interaction risk ratios (IRR) and 95% confidence intervals (CI), with BRCA (carrier vs. noncarrier) 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 noncarriers. 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, body mass index, 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 noncarriers. IMPACT: Advice to maintain a healthy weight, be physically active, and refrain from smoking will therefore benefit BRCA carriers as well as noncarriers.
Publisher: American Association for Cancer Research
Keywords: Female; Humans; Pregnancy; *BRCA1 Protein/genetics; *BRCA2 Protein/genetics; Mutation; *Ovarian Neoplasms/epidemiology/genetics; Risk Factors; Smoking/adverse effects
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1158/1055-9965.Epi-23-0984
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-07-09 04:13:26

Last Modified: 2024-07-09 04:14:11