Do U.S. county data disprove linear no-threshold predictions of lung cancer risk for residential radon?-A preliminary assessment of biological plausibility
Titel:
Do U.S. county data disprove linear no-threshold predictions of lung cancer risk for residential radon?-A preliminary assessment of biological plausibility
Auteur:
Bogen, Kenneth T.
Verschenen in:
Human and ecological risk assessment
Paginering:
Jaargang 3 (1997) nr. 2 pagina's 157-186
Jaar:
1997-05
Inhoud:
Lung-cancer mortality (LCM) is elevated in underground miners who chronically inhaled the mutagenic, cytotoxic α-decay products of radon gas. Epidemiologie studies of LCM rates vs. residential-radon concentration levels are generally considered inconclusive. However, Cohen (Health Physics 68, 157-174, 1995) has hypothesized that data on LCM vs. residential radon concentrations at the U.S. county level are clearly inconsistent with a linear no-threshold (LN) dose-response model, and rather are consistent with threshold or hormesis model. Cohen's hypothesis has been criticized as “ecological fallacy,”; particularly because LN (but not threshold or hormesis) models are generally considered biologically plausible for agents like α radiation that damage DNA in linear proportion to dose. To assess the biological plausibility of Cohen's hypothesis, a preliminary study was made of whether a biologically realistic, cytodynamic 2-stage (CD2) cancer model can provide a good, joint fit to Cohen's set of U.S. county data as well as to underground-miner data. The CD2 model used adapts a widely applied, mechanistic, 2-stage stochastic model of carcinogenesis to realistically account for interrelated cell killing and mutation (both assumed to have a LN dose-response), cell turnover, and incomplete exposure of stem cells. A CD2 fit was obtained to combined summary data on LCM vs. radon-exposure in white males in 1, 601 U.S. counties (from Cohen) and in white male Colorado Plateau (CP) uranium miners (from the National Research Council's “BEIRIV”; report). The CD2 fit is shown to: (i) be consistent with the combined data; (ii) have parameter values all consistent with biological data; and (iii) predict inverse dose-rate-effects data for CP and other radon-exposed miners, despite the fact that optimization had not involved any of these dose-rate data. The latter data were not predicted by a simplified CD2 model in which all stem cells were presumed to be exposed. It is concluded that this study provides preliminary evidence that Cohen's hypothesis is biologically plausible.
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