Multiomics Plasma Profiles for Early Detection of Breast Cancer within the UK Biobank

Description

Introduction: Breast cancer is a multifaceted disease and known as a leading contributor to cancer-related morbidity and mortality in females globally. In 2020 alone, 2.3 million women faced a diagnosis, while 685,000 cases were fatal. Biomarkers for early detection of breast cancer have the potential to complement population screening approaches to enable earlier and more precise treatment. The genome, proteome and metabolome serve as pivotal reservoirs for biomarker discovery. However, the identification of proteins and metabolites associated with breast cancer risk remains limited, but the UK Biobank holds huge potential to make discoveries in this area.
Methods: In this study we systematically reviewed publications in PubMed reporting on the existence of genomic, proteomic and metabolomic analyses in breast cancer within the UK Biobank. A meta-analysis of the genomic data was subsequently preformed using SNPnexus, GeneProtein in Cytoscape and Reactome. In tandem, multiomics analysis of UK Biobank plasma profiles (1461 proteins, n=25,000) and NMR-metabolite profiles (249 metabolites, n=55000) compared healthy controls verses incident breast cancer diagnosis (8373 of ∼500,000 UK Biobank participants), with a 14 year follow-up. To assess causality, multivariate statistics and Mendelian randomization were implemented, using cis-acting protein quantitative trait loci as instruments to combine datasets and detect discriminatory features that identify with differing cancer diagnoses.
Results: Our findings highlight the value of multiomic analysis within the UK Biobank. Breast cancer-associated genetic variants revealed known and unknown interconnected tumor-driven and tumor-supressor genes. This comprehensive analysis unveils associations among protein and metabolite levels, clinical characteristics, and gene variants.
Conclusions: This study identified the potential of harnessing multiomic strategies within the UK Biobank cohorts. Preliminary data underscores the power of a comprehensive multiomic profile in offering valuable insights into potential plasma biomarkers, identifying novel drug targets, and elucidating the biological mechanisms underlying breast cancer paving the way for early intervention strategies.

Period	18 Jun 2024
Event title	Metabolomics 2024
Event type	Conference
Location	Osaka, JapanShow on map
Degree of Recognition	International