Gene expression signatures of radiation exposure in peripheral white blood cells of smokers and non-smokers

Purpose: The issue of potential confounding factors is critical to the development of any approach to radiation biodosimetry, and has not been fully addressed for gene expression-based approaches. Materials and methods: As a step in this direction, we have investigated the effect of smoking on the global radiation gene expression response in ex vivo-irradiated peripheral blood cells using microarray analysis. We also evaluated the ability of gene expression signatures to predict the radiation exposure level of ex vivo-exposed samples from smokers and non-smokers of both genders. Results: We identified eight genes with a radiation response that was significantly affected by smoking status, and confirmed an effect of smoking on the radiation response of the four and a half LIM domains 2 (FHL2) gene using quantitative real-time polymerase chain reaction. The performance of our previously defined 74-gene signature in predicting the radiation dose to samples in this study was unaffected by differences in gender or smoking status, however, giving 98% correct prediction of dose category. This is the same accuracy as that found in the original study from which the signature was derived, using different donors. Conclusion: The results support the development of peripheral blood gene expression as a viable strategy for radiation biodosimetry.