Environmental Health Perspectives 105, Supplement 6, December 1997

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Curvilinearity in the Dose-Response Curve for Cancer in Japanese Atomic Bomb Survivors

Mark P. Little and Colin R. Muirhead

National Radiological Protection Board, Chilton, Oxon, United Kingdom

Abstract
Recently released data on cancer incidence in Japanese atomic bomb survivors are analyzed using a variety of relative risk models that take account of errors in estimates of dose to assess the dose response at low doses. If a relative risk model with a threshold (the dose response is assumed linear above the threshold) is fitted to solid cancer data, a threshold of more than about 0.2 Sv is inconsistent with the data, whereas these data are consistent with there being no threshold. Among solid cancer subtypes there is strong evidence for a possible dose threshold only for nonmelanoma skin cancer. If a relative risk model with a threshold (the dose response is assumed linear above the threshold) is fitted to the leukemia data, a threshold of more than about 0.3 Sv is inconsistent with the data. In contrast to the estimates for the threshold level for solid cancer data, the best estimate for the threshold level in the leukemia data is significantly different from zero even when allowance is made for a possible quadratic term in the dose response, albeit at borderline levels of statistical significance (p=0.04). There is little evidence for curvature in the leukemia dose response from 0.2 Sv upwards. However, possible underestimation of the errors in the estimates of the dose threshold as a result of confounding and uncertainties not taken into account in the analysis, together with the lack of biological plausibility of a threshold, makes interpretation of this finding questionable. -- Environ Health Perspect 105(Suppl 6):1505-1509 (1997)

Key words: cancer, leukemia, Japanese atomic bomb survivors, threshold, dose-response curve

This paper is based on a presentation at the International Conference on Radiation and Health held 3-7 November 1996 in Beer Sheva, Israel. Abstracts of these papers were previously published in Public Health Reviews 24(3-4):205-431 (1996). Manuscript received at EHP 28 February 1997; accepted 23 May 1997.

The authors are grateful for the detailed comments of the two referees. This report makes use of data obtained from the Radiation Effects Research Foundation (RERF) in Hiroshima, Japan. RERF is a private foundation funded equally by the Japanese Ministry of Health and Welfare and the U.S. Department of Energy through the U.S. National Academy of Sciences. The conclusions in this report are those of the authors and do not necessarily reflect the scientific judgment of RERF or its funding agencies. This work was funded partially by the Commission of the European Communities under contract FI4P-CT95-0009.

Address correspondence to Dr. M.P. Little, National Radiological Protection Board, Chilton, Didcot, Oxon, OX11 0RQ, U.K. Telephone: 044 1235 822806. Fax: 044 1235 833891. E-mail: mark.little@nrpb.org.uk

Abbreviations used: AAE, age at exposure; AML, acute myeloid leukemia; ERR, excess relative risk; GSD, geometric standard deviation; Gy, gray; ICRP, International Commission on Radiological Protection; LET, linear energy transfer; LSS, Life Span Study; RERF, Radiation Effects Research Foundation; Sv, sieverts; TSE, time since exposure.

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