Aging increases cancer risk and shapes immunity and prognosis. Circulating proteins reflect tissue states and intercellular signaling; their age-related changes may foreshadow disease. Leveraging UK Biobank’s plasma proteomics, genetics, and longitudinal health records, we aim to identify proteins linked to cancer initiation and outcomes, while accounting for lifestyle, environmental, and comorbidity factors.
Our project emphasizes causality and mechanism across four aims. Aim 1: identify proteins whose abundances vary with age and relate them to cancer incidence and mortality. Aim 2: integrate cancer GWAS with blood pQTL/eQTL to test causal effects between above proteins and cancer through Mendelian randomization. Aim 3: map candidate proteins to in-house peripheral-blood single-cell RNA-seq data from healthy individuals and untreated patients of different ages, defining the key immune subpopulations and examining enrichment in older patients with poor prognosis. Aim 4: validate findings in bulk transcriptomic cohorts and independent clinical biospecimens, including our Oxford OXCITE cohort, and perform mechanistic experiments. Additionally, we will explore the potential role of epigenetics by leveraging resources beyond UKB. Our lab’s strong research foundation in tumor immunology and epigenetics will also provide support for the study (e.g., Amir et al., Nature 2025. Wanqiang et al., Cell 2018).
This two-year program will integrate large-scale proteomics, human genetics, single-cell data, and laboratory validation to deliver actionable aging-linked targets at the interface of immunity and cancer. Distinct from correlation-driven signatures, our strategy prioritizes causal inference and mechanism, producing rigorously triaged proteins and cellular contexts supported by genetic and functional evidence. Outputs will include reproducible resources and guidance for risk stratification and early intervention in older adults, informing precision therapy.