Aim 1: Understanding Genetic Vulnerabilities
The first aim is to incorporate genetic susceptibility factors into the radon AOP, specifically focusing on DNA repair deficiencies. Genetic mutations in key DNA repair genes such as BRCA1, ATM, and XRCC1 can impair an individual ' s ability to correct the DNA damage induced by radon ' s alpha particles. Individuals carrying such mutations are at a greater risk of accumulating genetic errors that promote cancer initiation.
By modeling these genetic vulnerabilities within the AOP framework, we can better map how impaired DNA repair modifies the sequence of key events leading to lung cancer. This understanding will allow for a stratified risk assessment, identifying subpopulations who may be more vulnerable to radon exposure. Public health strategies could then be tailored to prioritize radon testing, education, and mitigation efforts for these high-risk groups, ultimately leading to more personalized and effective interventions.
Aim 2: Environmental Co-Exposures Amplify the Risk
The second aim focuses on expanding the radon AOP to incorporate the modifying effects of environmental co-exposures. In everyday environments, radon exposure often occurs alongside other hazardous exposures such as cigarette smoke, airborne particulate matter( PM2.5), and asbestos. These co-exposures can synergistically exacerbate radon-induced DNA damage, intensify oxidative stress, and enhance chronic inflammation, all key events in the pathway to lung cancer.
By systematically integrating environmental co-exposures into the AOP model, this research will enable a more realistic risk characterization reflective of real-world conditions. Such an enhanced AOP would allow regulators and policymakers to set context-specific radon action levels, particularly in environments where combined exposures significantly elevate lung cancer risk. It also underscores the importance of multi-hazard mitigation strategies in public health planning.
Aim 3: Bridging AOPs with Risk Management
The third aim is to assess the feasibility of translating the refined AOP into practical radon risk management tools and policies. This includes evaluating how AOP-informed insights about genetic vulnerabilities and environmental co-exposures can improve current risk assessment frameworks and intervention strategies.
This aim will involve reviewing existing radon regulations and guidelines from agencies like the EPA, WHO, and OECD, identifying opportunities where AOP-based understanding could strengthen policy design. The refined AOP could support new models for setting exposure thresholds, prioritizing high-risk regions and populations, and informing more dynamic, data-driven public health responses.