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Introduction
Ionizing radiation is an established risk factor for childhood acute leukemia (AL). This has been demonstrated by several studies, including the follow-up of survivors of the Hiroshima and Nagasaki atomic bombs (Hsu et al. 2013; Preston et al. 1994), studies of populations exposed therapeutically to radiation (Pearce et al. 2012; UNSCEAR 2000), and studies of populations exposed in utero (Doll and Wakeford 1997; Wakeford and Little 2003). The literature was recently extensively reviewed (Wakeford 2013). The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR 2006) and the Committee of the National Research Council of the United States on the Biological Effects of Ionizing Radiation (BEIR) (NRC 2006) have developed risk models that can be used to estimate leukemia risk associated with different patterns of radiation exposure (chronic or acute, external or internal).
Natural background radiation (NBR) leads to low-dose rates of exposure in the population. NBR comprises external exposure to cosmic and terrestrial gamma radiation and internal exposure by inhalation of radon gas and ingestion of radionuclides (UNSCEAR 2000). While dose from radon and its decay products is primarily delivered to the respiratory system, doses from terrestrial gamma and cosmic radiation are more homogeneously delivered throughout the body, including to the red bone marrow (RBM) (Kendall et al. 2009), which is thought to be the primary site of leukemia initiation.
Since the late 1980s, ecological studies in many countries have linked large-scale geographic variations in the incidence of AL with variations in average radon and gamma radiation exposure on that scale. As stated in several reviews (Laurier et al. 2001; Raaschou-Nielsen 2008; Tong et al. 2012), most of the studies found positive correlations with radon, whereas no evidence was found for gamma radiation exposure. Population-based case-control studies that included interviews and in-home measurements have reported mixed results, mostly nonsignificant (Raaschou-Nielsen 2008), but their interpretation is hindered by the generally limited participation rates and the subsequent potential for selection bias. More recently, record-based studies were developed on a nationwide scale in the general population, using modeled estimates of exposure to ionizing radiation and the geolocation of homes. A Danish record-based case-control study (Raaschou-Nielsen et al. 2008), which included 860 cases of AL, found an association between lifelong domestic radon exposure and AL...