A Task Group of the ICRP Committee 1 (Radiation Effects) has reviewed relevant data with the objective of advising the Main Commission of the ICRP on the possible implications for radiological protection of emerging views on genetic susceptibility to cancer. Chapters consider DNA damage, the mechanisms and genetics of solid tumours, lympho-haemopoietic tumours, commentary data and the development of computational modelling procedures that aim to describe the impact of genetic factors on radiation-tumorigenesis in human populations. The report is preliminary and serves principally to provide a framework on which to develop further views in this rapidly advancing area of human genetics.
Preface. Introduction. DNA Damage and Repair. The DNA damage spectrum after radiation. Post-irradiation cellular DNA repair and mutagenesis. Human genetic disorders affecting DNA repair and genomic instability. Summary and conclusions. Mechanisms and Genetics of Solid Tumours. Oncogenes. Tumour suppressor genes. DNA repair and replication genes in solid tumours. Genetic susceptibility to solid tumours. The origin of mutations in tumour-associated genes. The genetic component of solid tumours. Summary. Mechanisms and Genetics of Lympho-Haemopoietic Neoplasia. Mechanisms of induction of lympho-haemopoietic neoplasia. Genetic susceptibility to lympho-haemopoietic neoplasia. Summary and conclusions. Evidence on Associations Between Tumorigenic Radiosensitivity and Heritable Predisposition to Cancer. Mechanistic aspects of tumorigenic radiosensivity. Rodent models of cancer predisposition. Radiotherapeutic observation. Epidemiological aspects of tumorigenic radiosensitivity. Overall judgments on genetically determined tumorigenic radiosensitivity. Summary and conclusions. Computational Modeling of the Impact of Genetic Factors in Radiation Carcinogenesis. Familial cancer genes: estimates of mutant gene frequencies. Population genetic models of cancer predisposition and radiosensitivity. Implications For Radiological Protection of Data on Cancer Susceptibility. Familial cancer involving genes of high penetrance. Cancer involving genes of low penetrance. Areas of future research in radiological protection. The application of diagnostic technologies. Summary and conclusions for radiological protection.