Abstract 5896: Reproductive, hormonal and lifestyle correlates of circulating osteoprotegerin levels in women with a BRCA1 mutation

Abstract Purpose: BRCA1 mutation carriers face a very high lifetime risk of developing breast cancer. Dysregulation of the receptor activator of nuclear factor κB (RANK) pathway has been implicated in the pathogenesis of BRCA1-associated breast cancer. In addition, lower levels of osteoprotegerin (OPG), the decoy receptor for RANK-ligand, have been reported among women with a BRCA1 mutation and may be associated with an increased risk of breast cancer. Thus, inhibition of RANK signaling represents a potential target for prevention, and furthermore, OPG levels may be a biomarker of subsequent cancer risk. Whether non-genetic exposures also influence circulating levels of OPG in these high-risk women is not known. Therefore, the goal of this study was to evaluate reproductive, hormonal, and lifestyle correlates of OPG levels in BRCA1 mutation carriers. Methods: Eligible women included BRCA1 mutation carriers enrolled in a longitudinal study, aged 18 years or older, without a history of cancer, and with a serum sample available. All women completed a baseline questionnaire at the time of enrolment and a follow-up questionnaire every two years thereafter to collect detailed information on various exposures (i.e., reproductive, hormonal, and lifestyle) and outcomes. Serum OPG levels (pg/ml) were measured using an enzyme-linked immunosorbent assay (ELISA). Generalized linear models were used to evaluate the associations of various reproductive, hormonal, and lifestyle exposures at the time of blood collection with serum OPG and to estimate adjusted means. Results: A total of 828 women were included in the current analysis. Older age was associated with significantly higher OPG levels (<50 vs. >60 years, 79.04 vs. 82.01 pg/ml; Ptrend < 0.0001). Current vs. never smoking was also associated with significantly higher OPG levels (87.69 vs. 73.48 pg/ml; Pcat < 0.0001). There were no significant associations between other exposures and levels of OPG (P ≥ 0.17). Findings were similar in the analyses stratified by menopausal status. Conclusion: The results from this study suggest that non-genetic factors likely have a minimal impact upon serum OPG among women with a BRCA1 mutation. Further studies are needed to explore other potential correlates of OPG (i.e., diet, supplement use) and to elucidate whether integration of circulating OPG levels may improve existing risk prediction models. Citation Format: Sarah S. Park, Tasnim Zaman, Shana J. Kim, Jennifer D. Brooks, Andy K. Wong, Jan Lubiński, Steven A. Narod, Leonardo Salmena, Joanne Kotsopoulos. Reproductive, hormonal and lifestyle correlates of circulating osteoprotegerin levels in women with a BRCA1 mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5896.