Cancer risk from galactic cosmic radiation exposure is considered a potential "showstopper" for a manned mission to Mars. Calculating the actual risks that will be confronted by spaceflight crews is complicated by our limited understanding of the carcinogenic effects of high charge, high energy (HZE) ions, a radiation type for which there are no human epidemiological data. Here, we examine some of the assumptions underpinning the current NASA model used to assess space radiation cancer risk.
To study the effects of HZE ion irradiation in a genetically heterogeneous population, 1850 HS/Npt stock mice of both sexes were genotyped for 77,808 SNPs and exposed to (1) 0.4 Gy of 240 MeV/n 28Si ions or (2) 600 MeV/n 56Fe ions, (3) 3 Gy of 137Cs γ-rays, or (4) sham irradiated. The mice were monitored for cataractogenesis, cognitive deficits, and cancer development until they reached 800 days of age or became moribund. Comprehensive necropsies were performed on each mouse and on all organ systems. Each detected lesion was characterized histologically. Genome reconstructions, which provide the basis for genome-wide SNP imputation, were completed for each mouse using algorithms for probabilistic assembly of founder haplotypes. Polygenic covariance among related individuals was corrected for during quantitative trait loci (QTL) mapping using a kinship term and significance thresholds were determined with permutation tests. To appreciate shared susceptibility loci for multiple neoplastic phenotypes following exposure to HZE ions or γ-rays, LOD scores from each QTL were plotted as heatmaps and hierarchically clustered.
The spectrum of tumors induced by accelerator produced HZE ions is similar to the spectra of spontaneous and gamma-ray-induced tumors, though the proportions of specific tumors differ. Quantitative trait loci (QTL) controlling susceptibilities to spontaneous, γ-ray-induced, and HZE ion-induced tumors are identified, and cluster analyses based on coincident loci point to share susceptibility loci for specific tumors types regardless of their origins (how they were induced). Malignancy, as measured by decreased latency or increased metastatic density, is comparable for radiation-induced and spontaneous tumors. Female mice are at a greater risk for radiogenic tumors than male mice. These findings support the assumptions underlying the current model used by NASA to estimate fatal cancer risks from space radiation exposures.