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

• Published in: British journal of cancer Vol. 117; no. 1; pp. 41 - 50
• Main Authors: Chernyavskiy, Pavel, Edmondson, Elijah F, Weil, Michael M, Little, Mark P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.06.2017; Nature Publishing Group
• Subjects: 692/499; 692/699/67/1059/485; 692/699/67/1612; 692/699/67/1990/283/1897; Adenocarcinoma; Adenocarcinoma - etiology; Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adenoma - etiology; Adenoma - genetics; Adenoma - mortality; Animals; Background radiation; Biomedical and Life Sciences; Biomedicine; Breeding; Cancer Research; Carcinoma, Hepatocellular - etiology; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - mortality; Drug Resistance; Epidemiology; Exposure; Gamma rays; Gamma Rays - adverse effects; Harderian Gland; Health risk assessment; Health risks; Hepatocellular carcinoma; Ions; Irradiation; Leukemia; Leukemia, Myeloid - etiology; Leukemia, Myeloid - genetics; Leukemia, Myeloid - mortality; Liver Neoplasms, Experimental - etiology; Liver Neoplasms, Experimental - genetics; Liver Neoplasms, Experimental - mortality; Lung cancer; Lung Neoplasms - etiology; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Mice; Molecular Medicine; Neoplasms - etiology; Neoplasms - genetics; Neoplasms - mortality; Neoplasms, Radiation-Induced - genetics; Neoplasms, Radiation-Induced - mortality; Neoplastic Syndromes, Hereditary - etiology; Neoplastic Syndromes, Hereditary - genetics; Neoplastic Syndromes, Hereditary - mortality; Oncology; Periodicity; Proportional Hazards Models; Radiation, Ionizing; Risk assessment; Risk factors; Sebaceous Gland Neoplasms - etiology; Sebaceous Gland Neoplasms - genetics; Sebaceous Gland Neoplasms - mortality; Translational Therapeutics; Tumors; γ Radiation; lung cancer; familial clustering; high-energy beam; ionising radiation; myeloid leukaemia; space radiation exposure; mice
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2017.141

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.