Epidemiologic issues related to nasopharyngeal radium exposures

A number of topics are discussed related to the potential for and pitfalls in undertaking epidemiologic studies of the late effects of nasopharyngeal radium irradiation. The available evidence indicates that linear extrapolation of risk estimates from high-dose studies is a reasonable basis for estimating risk from radium exposure or other situations in which the radiation exposures were fairly low and fractionated. Epidemiologic study of populations given nasopharyngeal radium irradiation is worthwhile scientifically if several criteria can be met. It is very important that any such study has adequate statistical power, which is a function of the doses to the organs of interest and the radiation risk coefficients for those organs, as well as the available sample size. If the organ doses are low, a prohibitively large sample size would be required. Other problems with low-dose studies include the likelihood of false-positive results when a number of health end points are evaluated and the impact of dose uncertainties, small biases, and confounding factors that make the interpretation uncertain. Cluster studies or studies of self-selected cohorts of irradiated patients are not recommended because of the potential for severe bias with such study designs. The ability to define subgroups of the population who have heightened genetic susceptibility may become a reality in the next few years as genes conferring susceptibility to brain cancers or other head and neck tumors are identified; this scientific advance would have the potential to alter greatly the prospects and approaches of epidemiologic studies.