title: Dose-effect relationships, epidemiological analysis and the derivation of low dose risk.
abstract: This paper expands on our recent comments in a letter to this journal about the analysis of epidemiological studies and the determination of low dose RBE of low LET radiation (Chadwick and Leenhouts 2009 J. Radiol. Prot. 29 445-7). Using the assumption that radiation induced cancer arises from a somatic mutation (Chadwick and Leenhouts 2011 J. Radiol. Prot. 31 41-8) a model equation is derived to describe cancer induction as a function of dose. The model is described briefly, evidence is provided in support of it, and it is applied to a set of experimental animal data. The results are compared with a linear fit to the data as has often been done in epidemiological studies. The article presents arguments to support several related messages which are relevant to epidemiological analysis, the derivation of low dose risk and the weighting factor of sparsely ionising radiations. The messages are: (a) cancer incidence following acute exposure should, in principle, be fitted to a linear-quadratic curve with cell killing using all the data available; (b) the acute data are dominated by the quadratic component of dose; (c) the linear fit of any acute data will essentially be dependent on the quadratic component and will be unrelated to the effectiveness of the radiation at low doses; consequently, (d) the method used by ICRP to derive low dose risk from the atomic bomb survivor data means that it is unrelated to the effectiveness of the hard gamma radiation at low radiation doses; (e) the low dose risk value should, therefore, not be used as if it were representative for hard gamma rays to argue for an increased weighting factor for tritium and soft x-rays even though there are mechanistic reasons to expect this; (f) epidemiological studies of chronically exposed populations supported by appropriate cellular radiobiological studies have the best chance of revealing different RBE values for different sparsely ionising radiations.
authors.forename: H P
authors.initials: HP
authors.lastname: Leenhouts
authors.forename: K H
authors.initials: KH
authors.lastname: Chadwick
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D002869:Chromosome Aberrations / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004583:Electrons; D005720:Gamma Rays; D006801:Humans; D007564:Japan / Q000453:epidemiology; D018499:Linear Energy Transfer / Q000528:radiation effects*; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology*; D009689:Nuclear Warfare; D016273:Occupational Exposure / Q000009:adverse effects; D011829:Radiation Dosage; D012062:Relative Biological Effectiveness; D017741:Survivors; D014965:X-Rays