Ionizing radiation and genetic risks. XIII. Summary and synthesis of papers VI to XII and estimates of genetic risks in the year 2000.
This paper recapitulates the advances in the field of genetic risk estimation that have occurred during the past decade and using them as a basis, presents revised estimates of genetic risks of exposure to radiation. The advances include: (i) an upward revision of the estimates of incidence for Mendelian diseases (2.4% now versus 1.25% in 1993); (ii) the introduction of a conceptual change for calculating doubling doses; (iii) the elaboration of methods to estimate the mutation component (i.e. the relative increase in disease frequency per unit relative increase in mutation rate) and the use of the estimates obtained through these methods for assessing the impact of induced mutations on the incidence of Mendelian and chronic multifactorial diseases; (iv) the introduction of an additional factor called the "potential recoverability correction factor" in the risk equation to bridge the gap between radiation-induced mutations that have been recovered in mice and the risk of radiation-inducible genetic disease in human live births and (v) the introduction of the concept that the adverse effects of radiation-induced genetic damage are likely to be manifest predominantly as multi-system developmental abnormalities in the progeny. For all classes of genetic disease (except congenital abnormalities), the estimates of risk have been obtained using a doubling dose of 1 Gy. For a population exposed to low LET, chronic/ low dose irradiation, the current estimates for the first generation progeny are the following (all estimates per million live born progeny per Gy of parental irradiation): autosomal dominant and X-linked diseases, approximately 750-1500 cases; autosomal recessive, nearly zero and chronic multifactorial diseases, approximately 250-1200 cases. For congenital abnormalities, the estimate is approximately 2000 cases and is based on mouse data on developmental abnormalities. The total risk per Gy is of the order of approximately 3000-4700 cases which represent approximately 0.4-0.6% of the baseline frequency of these diseases (738,000 per million) in the population.
Sankaranarayanan
K
K
Sylvius Laboratories, Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Center, Wassenaarseweg 72, 2333, AL Leiden, The Netherlands. sankaran@rulf2.medfac.leidenuniv.nl
Chakraborty
R
R
D000818:Animals; D000013:Congenital Abnormalities / Q000209:etiology; D030342:Genetic Diseases, Inborn / Q000209:etiology*; D006801:Humans; D007564:Japan; D051379:Mice; D009154:Mutation; D009689:Nuclear Warfare; D011839:Radiation, Ionizing