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Derivation of low-dose extrapolation factors from analysis of curvature in the cancer incidence dose response in Japanese A-bomb survivors

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The derivation of cancer risks after low-dose and low-dose-rate exposure to ionising radiation is critical to the setting of standards for radiological protection. In extrapolating cancer risks observed in groups exposed at a high dose-rate such as the Japanese A-bomb survivors, the International Commission on Radiological Protection (ICRP) recommends application of a Dose and Dose-Rate Effectiveness Factor (DDREF) of 2 to obtain cancer risks at low doses and low dose-rates. In this paper, the degree of overestimation in low-dose cancer risk when models linear in dose are fitted to cancer data was assessed by examination of the quadratic and the linear coefficients (in dose) in the Japanese A-bomb survivor cancer incidence data, taking separate account of random errors in DS86 neutron and DS86 gamma dose estimates and systematic errors in Hiroshima DS86 neutron dose estimates. When the 0–4 Gy dose range is used, the low-dose extrapolation factor for all solid tumours, assessing the degree to which low-dose cancer risks are overestimated by fitting a model linear in dose, is 1.06 (95% CI 0.78, 1.62) and so is not significantly different from 1. The best estimate of the low-dose extrapolation factor for leukaemia is 2.47 (95% CI 1.24, >1000). When various types and groupings of solid tumours are considered, there is not generally any strong evidence for upward curvature; for only two out of the six solid tumour groupings are there indications of appreciable upward curvature in the dose response, and in no instance is this statistically significant. Consideration of a lower dose range (0–2 Gy rather than 0–4 Gy) results in the low-dose extrapolation factor for solid tumours increasing to 1.21 (95% CI 0.81, 2.45), with corresponding increases for solid tumour subtypes; the corresponding quantity for leukaemia decreases to 1.73 (95% CI 0.79, 147.67). Three out of the six solid tumour subtypes now show appreciable upward curvature. If there is additional adjustment of the Hiroshima neutron dose estimates over the 0–2 Gy dose range, the low-dose extrapolation factor for all solid tumours increases still further to 1.43 (95% CI 0.97, 2.72), whereas for leukaemia this quantity is further reduced to 1.58 (95% CI 0.90, 10.58). The minor discrepancy between the DDREF of 2 recommended by the ICRP and the estimate of the low-dose extrapolation factor of about 1.5 that is derived here for solid tumours and leukaemias is unremarkable.

Keywords: A-bomb survivors, dose and dose-rate effectiveness factor, DDRF, Japan, leukaemia, dosimetric error, solid tumors, cancer risks, ionising radiation, radiological protection

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