Risk coefficients for childhood cancer after intrauterine irradiation: a review

PURPOSE: To review the estimates of the risk of childhood cancer per unit dose of radiation received in utero derived from the largest case-control study of obstetric X-ray examinations and to compare them with the childhood cancer risk coefficients obtained from the cohorts of Japanese atomic bomb survivors irradiated either in utero or as young children. MATERIALS AND METHODS: Data from the Oxford Survey of Childhood Cancers (OSCC) case-control study of foetal exposure to diagnostic X-rays and from the cohort studies of the Japanese survivors of the atomic bombings of Hiroshima and Nagasaki were used, together with associated dose estimates. Excess relative risk and excess absolute risk coefficients were compared, fully taking into consideration the various sources of uncertainty. RESULTS: The excess relative risk coefficient for childhood (< 15 years of age) cancer obtained from the OSCC was around 50 Gy(-1), leading to an excess absolute risk coefficient for incident cases of about 8% Gy(-1). However, the statistical, dosimetry, modelling and other uncertainties associated with these risk estimates are appreciable, and there is reason to believe that these coefficients could be systematic overestimates. When these uncertainties and those associated with the equivalent risk coefficients derived from the Japanese cohort exposed in utero are taken into account, the risk estimates for childhood cancer obtained from these two sources are compatible. These coefficients are consistent with the high relative risk of childhood leukaemia among the Japanese survivors exposed as children. The absence of cases of childhood solid tumours among the Japanese children irradiated after birth in contrast to the significant excesses found in both intrauterine exposure studies might be explained by the cells from which these cancers originate being predominantly sensitive only to exposure in utero. CONCLUSIONS: The consistency of the childhood cancer risk coefficients derived from the Oxford Survey and from the Japanese cohort irradiated in utero supports a causal explanation of the association between childhood cancer and an antenatal X-ray examination found in case-control studies. This implies that doses to the foetus in utero of the order of 10 mSv discernibly increase the risk of childhood cancer. However, uncertainties in risk estimates are such that it is difficult to conclude reliably from these epidemiological data what the level of risk at these low doses might be, beyond the inference that the risk is not zero or has been grossly underestimated.