Evaluation of Circulating Plasma Proteins in Breast Cancer: A Mendelian Randomization Analysis

Abstract The blood proteome reflects homeostatic and dynamic cellular processes across human organs. However, few blood proteomics studies of sufficient depth and size have been reported in breast cancer. To comprehensively identify circulating proteins with a causal role in breast cancer we measured 2,929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project and explored associations between proteins levels, clinical characteristics, and gene variants. The analysis revealed 812 cis-acting protein quantitative trait loci (pQTL), which were used as instruments in Mendelian randomisation (MR) analysis of breast cancer. Five proteins (P < 1.7x10-5, Bonferroni-corrected) with a potential causal role in breast cancer risk were revealed (CD160, DNPH1, LAYN, LRRC37A2 and TLR1). Confirming the MR findings in independent cohorts (FinnGen R9 and the UK Biobank), our study suggests that these proteins should be further explored as potential drug targets in breast cancer.