Circulating RANKL, Osteoprotegerin and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Emerging evidence demonstrates the receptor activator of nuclear factor κB (RANK) signaling is of importance in BRCA-associated breast cancers. BRCA mutation carriers face a high lifetime risk of developing breast cancer and have been reported to have lower levels of osteoprotegerin (OPG) and RANK ligand (RANKL) compared to non-carriers. OPG has been associated with decreased breast cancer risk among mutation carriers in a small pilot study. Circulating RANKL has yet to be explored in this high-risk population. My thesis investigated the association between circulating OPG and RANKL and breast cancer risk in mutation carriers. There is a suggestive trend demonstrating an inverse association between circulating OPG and BRCA breast cancer risk. However, circulating RANKL levels are not predictive of BRCA breast cancer risk. OPG could be a novel biomarker for breast cancer risk among BRCA mutation carriers and may provide a novel target for chemoprevention.M.Sc