High-energy particle beam and gamma radiation exposure, familial relatedness and cancer in mice

BACKGROUND: Some highly penetrant familial cancer syndromes exhibit elevated leukaemia risk, and there is evidence for familial clustering of lung cancer and other common cancers. Lung cancer and leukaemia are strongly radiogenic, but there are few indications that high-energy beam irradiation is markedly more effective than lower-energy radiation. METHODS: We used a Cox model with familially structured random effects to assess 16 mortality end points in a group of 1850 mice in 47 families maintained in a circular-breeding scheme, exposed to accelerated Si or Fe ions (0.4 Gy) or (137)Cs gamma rays (3 Gy). RESULTS: There is periodicity in the effect of familial relatedness, which is most pronounced for pulmonary adenoma, Harderian-gland adenoma, Harderian-gland tumour, ectodermal tumour, pulmonary adenocarcinoma and hepatocellular carcinoma (P=0.0001/0.0003/0.0017/0.0035/0.0257/0.0340, respectively) with families that are 3–4 generations apart most strongly correlated; myeloid leukaemia also exhibited a striking periodic correlation structure. The relative risks of high-energy Si or Fe ions are not significantly different and are less than for (137)Cs gamma-rays for most end points at the doses used. CONCLUSIONS: There is periodicity in the effect of familial relatedness for various cancer sites. The effects per unit dose of high-energy charged particle beams are no higher than ninefold those of lower-energy gamma radiation.