ICRP Publication 79: Genetic Susceptibility to Cancer
Annals of the ICRP Volume 28/1-2By
- . ICRP
ICRP Publication 79 provides an extensive discussion of hereditary variations in the susceptibility to cancer, and includes a commentary on the possible implications of such susceptibility variations for radiological protection. Current ICRP recommendations are based essentially on the estimation of excess cancer risk after exposure of whole populations. Because of differences in genetic make-up between individuals, there is a strong expectation that the excess cancer risk per unit dose of radiation exposure will be non-uniform. The report seeks to review relevant data and make interim judgments on tumorigenic radiosensitivity in the genetic disorders of this type, and also on the likely contribution that genetic factors may make to radiation-induced cancer. Since directly informative epidemiological data on radiation effects under differing cancer predispositions are essentially lacking, emphasis is placed on experimental studies and clinical observations, on computational genetic models of cancer risk, and on possible research strategies for the future. This provides a framework facilitating future judgments in this rapidly advancing area of human genetics. At this stage, the utility of genetic testing for cancer predisposition is limited by technical factors and concerns on predictive power. The preliminary conclusion is that in the future, genetic testing may find selected use prior to certain medical exposures to radiation, but apart from that, genetic testing for cancer disorders seems unlikely on current knowledge to attain a major role in radiation protection practice.
International Commission on Radiological Protection
Published: May 1999
...this is a long, and in some places highly technical report, but for the reader with even a modest background knowledge of radiobiology and molecular biology, it provides a most useful, and thought provoking review of the current state of knowledge in a field that is not only of medical and scientific importance, but raises important ethical issues which ultimately must be addressed by society at large...
D.M. Taylor, Radiation Protection Dosimetry, Vol. 86, No. 3, 1999
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.