Correlates of Circulating Osteoprotegerin in Women with a Pathogenic or Likely Pathogenic Variant in the BRCA1 Gene

Background: Lower levels of osteoprotegerin (OPG), the decoy receptor for receptor activator of NF kappa B (RANK)-ligand, have been reported among women with a BRCA1 mutation, suggesting OPG may be marker of cancer risk. Whether various reproductive, hormonal, or lifestyle factors impact OPG levels in these women is unknown. Methods: BRCA1 mutation carriers enrolled in a longitudinal study, no history of cancer, and a serum sample for OPG quantification, were included. Exposure information was collected through self-reported questionnaire at study enrollment and every 2 years thereafter. Serum OPG levels (pg/mL) were measured using an ELISA, and generalized linear models were used to assess the associations between reproductive, hormonal, and lifestyle exposures at the time of blood collection with serum OPG. Adjusted means were estimated using the fully adjusted model. Results: A total of 701 women with a median age at blood collection of 39.0 years (18.0-82.0) were included. Older age (Spearman r = 0.24; P < 0.001) and current versus never smoking (98.82 vs. 86.24 pg/mL; P-cat < 0.001) were associated with significantly higher OPG, whereas ever versus never coffee consumption was associated with significantly lower OPG (85.92 vs. 94.05 pg/mL; P-cat = 0.03). There were no other significant associations for other exposures (P >= 0.06). The evaluated factors accounted for 7.5% of the variability in OPG. Conclusions: OPG is minimally influenced by hormonal and lifestyle factors among BRCA1 mutation carriers. Impact: These findings suggest that circulating OPG levels are not impacted by non-genetic factors in high-risk women.