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12 Genetic Susceptibility and Radiological Health and Safety
- Johns Hopkins University Press
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C H A P T E R 12 Genetic Susceptibility and Radiological Health and Safety KENNETH L. MOSSMAN With the publication of the complete human genome in 2001, the door has been pushed wide open to explore fully the genetic basis of human disease. DNA specimens from many individuals can now be examined to identify variants in the 25,000 to 30,000 genes now believed to make up the human genome. Today, DNA chip technology is capable of scanning tens of thousands of genetic variants. Routine genetic screening is just a matter of time. Recognizing and cataloging genetic variants will help to identify specific genes that influence vulnerability to a wide spectrum of human diseases including cancer. Methods of identifying genetic markers for disease , in combination with pathophysiologic studies, will aid in developing diagnostic tests for early detection and individualized therapies. But individuals known to be at risk for specific diseases through genetic screening could be subject to employment, insurance, and social discrimination. A significant number of genetically based diseases have now been identified that confer heightened cancer risk (Sankaranarayanan and Chakraborty, 2001). This chapter explores individual cancer sensitivity, with a focus on radiation-induced cancer in the workplace environment. More is known about the cancer-causing effects of ionizing radiation than any other human carcinogen, except perhaps tobacco smoke. There is substantial experience in control of ionizing radiation exposure in the workplace. Management of exposure of the pregnant worker serves as a useful model in developing management strategies for radiosensitive individuals . The developing embryo or fetus is more sensitive to radiation than is the adult. Although pregnancy is a temporary condition, current policies to protect the developing fetus may be of value in developing guidance for protecting workers who are found to be genetically predisposed to cancer. An individual’s sensitivity to ionizing radiation exposure has emerged as an important consideration in protecting workers and members of the public. Identifying radiation-sensitive individuals (through medical screening or disease diagnosis) and providing them with adequate protection raise important policy questions. Who Is Sensitive to Radiation? Radiosensitivity (i.e., the response of an individual to a given dose of ionizing radiation) can be defined statistically by the frequency distribution of sensitivities in the population or by the severity of cancer by cancer site. Genetic mutations and polymorphisms have emerged as an important area of research to elucidate the underlying basis of variations in individual cancer sensitivities (National Research Council, 2007). Depending on the underlying genetic mutation, an individual may be at a greater risk than others for lung cancer, breast cancer, colorectal cancer, thyroid cancer, or other cancers from exposure to ionizing radiation. Because cancers have different incidence and mortality rates and present different clinical management challenges (American Cancer Society, 2005), consequences of workplace exposures may be more severe in one person than in another. Having any form of cancer is unfortunate, but certain cancers are more clinically significant than others. Although little evidence is available at this time, sensitivity to radiation may also imply sensitivity to chemical carcinogens, if those sensitivities are determined by common damage and repair pathways. The proportion of workers and the public who have increased radiogenic cancer risk because of genetic susceptibility is not known but has been estimated to be in the range of 1 to 10 percent. The proportion of G E N E T I C S U S C E P T I B I L I T Y A N D R A D I A T I O N 203 [44.200.240.205] Project MUSE (2024-03-29 10:10 GMT) the population that is radiosensitive is difficult to determine directly because of the nonspecificity of radiogenic diseases and because of the small radiation doses received occupationally and by the general population (Mossman, 1997; International Commission on Radiological Protection, 1998). It is assumed that individual sensitivities vary in accordance with a normal distribution and that radiosensitivity is normally distributed in the population as are height and other biological characteristics (Figure 12.1). Most people have a radiosensitivity that clusters around a central estimate (in the figure, the central estimate is 50 relative radiosensitivity units, assuming radiation sensitivity in the population varies from 1 to 100 relative units). Individuals with sensitivities that deviate significantly from the central estimate or average are termed to be either radioresistant or radiosensitive. As an illustration, the darkened region in Figure 12.1 represents 10 percent of...