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Introduction to Radiation Health: Late Effects - Cancer. Dr. Niel Wald. Radiobiological Effects. Non-Stochastic Severity varies with dose May have threshold (cataract, dermatitis) Stochastic Probability of occurrence in population varies with dose No threshold (cancer, genetic damage).
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Introduction to Radiation Health: Late Effects - Cancer Dr. Niel Wald
Radiobiological Effects • Non-Stochastic • Severity varies with dose • May have threshold (cataract, dermatitis) • Stochastic • Probability of occurrence in population varies with dose • No threshold (cancer, genetic damage) 227-4
395-4 Classification of Neoplasms
Tumor Growth Curve 395-6
Scheme for Induction of Cancer by Environmental Carcinogens Normal Cells Initiator(s) (electrophilic, mutagenic) Chemical or Radiation Carcinogen Initiated Cells Tumor Cells Promoter(s) Clones Inactive Metabolites Gross Tumors 395-11 Courtesy of Miller and Miller
Histogenetic Classification of Malignant Tumors with Atypical Nomenclature: 642-2(2)
Mechanisms of Cell Death 642-3
Maturation Arrest 642-6
Metastasis Formation 666-2
Metastasis Formation 666-3
Cancer Development 395-16
General Properties of Initiating Agents & Promoting Agents *defined in a broad sense as agents that can both initiate cancer in limited dosages and induce cancer in higher dosages or in states of increased host susceptibility 395-15
Properties of Oncogenes and Tumor Supressor Genes 666-9 * From Rudden, 1995b, with permission.
Cancer Summary • Tissues vary considerably with respect to their sensitivity to cancer induction. • The major sites of solid tumors induced by whole-body exposure to radiation are the breast, thyroid, lung and digestive organs. • Age, both at the time of exposure and diagnosis, is a very important variable relating to cancer induction. • The latency period (time from exposure to tumor detection) is frequently very long, i.e. years to decades. • Interaction between host and environmental factors (i.e., hormonal influences, exposure to other carcinogenic agents) may play a significant role in tumor induction. • Nearly all the tissues in the body are susceptible to tumor induction. • The dose-response relationships for many animal model systems are qualitatively similar to those for human tumor induction. However, direct quantitative risk extrapolation from animals to man would be inappropriate 395-28
Absolute Risk Model 220-4
Relative Risk Model 220-5
The quadratic risk coefficient () has increased, whereas the linear low-dose risk coefficient () has decreased, suggesting that currently accepted standards for low-level gamma exposures are not in need of revision on the basis of changes in data from Japan. Risk Coefficients for Leukemia Mortality Risk Coefficient 10 rad (Cases/106/year/rad)100 rad Source: Adapted from Straume and Dobson (1981). Reproduced from Health Physics, Vol. 44 by permission of the Health Physics Society 303-4
The observed and expected numbers of Ankylosing Spondylitis deaths due to leukemia and aplastic anemia, 1935 - 54 study series Number of Deaths Significance of difference between observed and maximum expected number of deaths: Leukemia: P < 0.000001 Aplastic anemia: P < 0.000001 104-E
Risk of Leukemia in various Diseases and Conditionsa,b a Risk of leukemia in various groups with specific epidemiologic and pathologic characteristics in populations followed for 10-30 years. b Leukemia risk (lifetime): Mortality increment from single exposure to 1 rad is 15-25 cases/106 persons or ~ 1/50,000. c Free in air doses (rads): gamma rays > 500 rads; neutrons > 60 rads Source: Modified from Miller (1970; from Brent (1980) 303-5
Leukemia Risk 96-I
Thyroid Cancer Risk Associated with I-131 Exposure from Chernobyl Estimated Thyroid Dose from I-131 (Gy) Adapted from Astakhova et al., 1998 668-5