Human Lung Cancer Risks from Radon – Part III - Evidence of Influence of Combined Bystander and Adaptive Response Effects on Radon Case-Control Studies - A Microdose Analysis

Abstract

ᮀ Since the publication of the BEIR VI (1999) report on health risks from radon, a significant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, in particular the potentially deleterious Bystander Effect (BE) and the potentially beneficial Adaptive Response radio-protection (AR). The case-control radon lung cancer risk data of the pooled 13 European countries radon study (Darby et al 2005(Darby et al , 2006) and the 8 North American pooled study (Krewski et al 2005(Krewski et al , 2006) have been evaluated. The large variation in the odds ratios of lung cancer from radon risk is reconciled, based on the large variation in geological and ecological conditions and variation in the degree of adaptive response radio-protection against the bystander effect induced lung damage. The analysis clearly shows Bystander Effect radon lung cancer induction and Adaptive Response reduction in lung cancer in some geographical regions. It is estimated that for radon levels up to about 400 Bq m -3 there is about a 30% probability that no human lung cancer risk from radon will be experienced and a 20% probability that the risk is below the zero-radon, endogenic spontaneous or perhaps even genetically inheritable lung cancer risk rate. The BEIR VI (1999) and EPA (2003) estimates of human lung cancer deaths from radon are most likely significantly excessive. The assumption of linearity of risk, by the Linear No-Threshold Model, with increasing radon exposure is invalid.

Human Lung Cancer Risks from Radon – Part II – Influence from Combined Adaptive Response and Bystander Effects – a Microdose Analysis

“…Here we used – cosmic rays 1.00 mSv; Terrestrial gamma 0.60 mSv (U gamma 0.146 mv; Th gamma 0.234 mSv; K-40 gamma 0.220 mSv); internal 0.80 mSv; and medical 1.20 mSv. These large variations support a large variation in human lung cancer risks for the case-control studies shown in Figures 2A and 2B of Part I (Leonard et al 2009a), which are further studied in Part III (Leonard et al 2009b). The normalized alpha particle representative dose response given in Figure 16 of Part I further support a non-linear BaD Model type dose response in the large variations in Figures 16 and 17.…”

“…The normalized alpha particle representative dose response given in Figure 16 of Part I further support a non-linear BaD Model type dose response in the large variations in Figures 16 and 17. This will be shown to be true, in Part III (Leonard et al 2009b), for the case-control studies. There is a difference relative to the expected dose response from case-control studies and what we have predicted in Figures 16 and 17 for combined bystander and adaptive response effects.…”

“…We show their data as Figure 4B. We will discuss other very recent data, primarily from Dr. Ron Mitchels research group (Mitchel et al 1999, 2002, 2003, 2004, Mitchel 2006, 2007a, 2007b, 2008), showing the persistence of AR effects in vivo for much longer times in the later Discussion sections of Part III (Leonard et al 2009b). It may be that AR is sustained longer in vivo than in tissue cultures where immortalized cells are used.…”

“…Thus a representative alpha particle dose response shape is obtained which should be applicable to the alpha particle dose response in human lung tissue. This representative alpha particle dose response is shown in Figure 10 of Part I (Leonard et al 2009b). It is then normalized to the Figure 3-2, of BEIR VI (1999), estimated lung cancer Relative Risk at 400 Bq m −3 , believed to be reliable for both the case-control and underground miners lung risk data.…”