An Evolving New Paradigm for Assessing the Risk of Radiation-Induced Cancer (Radcancer)

Background The International Commission on Radiological Protection’s system of radiological protection (SRP) is mainly based on the linear no-threshold (LNT) hypothesis for radiation-induced cancer (radcancer). Objective To further demonstrate the invalidity of the LNT hypothesis for total-cancer absolute risk AR ( D ) as a function of the above natural background radiation absorbed dose D and provide a theoretical foundation for an improved SRP, based on a nonlinear threshold dose-response relationship for radcancer absolute risk AR r ( D ). Approach Use high signal-to-noise ratio (SNR) pituitary-tumor cancer-prevention data from a gamma-ray study with > 15000 mice and Bayesian-inference-related stochastic-threshold modeling to characterize the dose-response relationships for the total cancer prevention TP ( D ) probability, AR ( D ) (=1 – TP ( D )), and AR r ( D ). Results A non-monotonic relationship for TP ( D ) and a population-threshold ( D t )-multimodal relationship for AR r ( D ) were found, which represent dose-response shapes for these endpoints for all cancer types, for the dose range modeled. For D < D t only hormetic outcomes ( TP ( D ) > P 0 ) occur, where P 0 is the genomic-stress-adaptation (gensadaptation)-linked baseline cancer prevention probability. Conclusions AR r ( D ) is not an LNT or linear-quadratic or sigmoidal function of dose. Below D t , D can reduce the population exposome-histories (expohistories)-related baseline-cancer absolute risk AR 0 .