This study aims to assess the relative contributions of environmental (e.g., smoking, diet, pollution) and genetic (polygenic risk scores, rare variants) factors to cancer risk across tumor types, while testing for gene-environment interactions and identifying high-risk subgroups where genetic predisposition amplifies environmental effects. While GWAS studies suggest genetics explains 5-30% of cancer risk, most cancers are environmentally driven-yet prior studies lack comprehensive exposure data, ignore interactions, and focus on single cancers. Leveraging UK Biobank’s detailed lifestyle, biomarker, and genetic data, we will (1) quantify population-attributable fractions of key risk factors, (2) model statistical interactions, and (3) stratify risk to inform precision prevention strategies.
