Allostatic load is a composite measure of multisystem physiological stress and has been linked to chronic disease, accelerated aging and mortality. Recent analyses in clinical cancer cohorts have shown that cancer modulated allostatic load, derived from longitudinal biomarker trajectories, is associated with overall survival and with specific genomic features in certain tumor types including non small cell lung cancer. The goal of this project is to investigate whether similar relationships can be observed in a large population cohort and to evaluate how chronic physiological stress relates to cancer incidence, progression and mortality at population scale.
The objectives are to measure allostatic load using biomarker panels available in UK Biobank, model longitudinal stress trajectories when repeated biomarkers are available and evaluate associations with incident cancer, cancer specific mortality and all cause mortality. We will examine whether germline variation in genomic regions related to lung cancer risk including the EGFR, KRAS and STK11 loci modifies the relationship between allostatic load and cancer outcomes. Additional analyses will include mediation models incorporating lifestyle, comorbidity burden and socioeconomic factors.
This work aims to clarify how chronic physiological stress interacts with inherited genomic variation to influence cancer onset and prognosis. The findings may improve risk prediction and support the development of integrated biomarkers for early identification of high risk individuals in the general population.