Biomedical subjects
Publications and source records attributed to R Wakeford.
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The association between the low dose of ionizing radiation received by the fetus in utero from diagnostic radiography, particularly in the last trimester of pregnancy, and the subsequent risk of cancer in childhood provides direct evidence against the existence of a threshold dose below which no excess risk arises, and has led to changes in medical practice. Initially reported in 1956, a consistent association has been found in many case-control studies in different countries. The excess relative risk obtained from combining the results of these studies has high statistical significance and suggests that, in the past, a radiographic examination of the abdomen of a pregnant woman produced a proportional increase in risk of about 40%. A corresponding causal relationship is not universally accepted and this interpretation has been challenged on four grounds. On review, the evidence against bias and confounding as alternative explanations for the association is strong. Scrutiny of the objections to causality suggests that they are not, or may not be, valid. A causal explanation is supported by evidence indicating an appropriate dose-response relationship and by animal experiments. It is concluded that radiation doses of the order of 10 mGy received by the fetus in utero produce a consequent increase in the risk of childhood cancer. The excess absolute risk coefficient at this level of exposure is approximately 6% per gray, although the exact value of this risk coefficient remains uncertain.
The results of a previous study suggested that an association between childhood leukaemia and the radiation dose received occupationally by a father before the conception of his child might provide the explanation for the marked excess of childhood leukaemia and non-Hodgkin's lymphoma in the village of Seascale, West Cumbria. The present study identifies other small areas (electoral wards) in West Cumbria where excess cases of leukaemia and non-Hodgkin's lymphoma in young people have occurred and determines whether a recorded dose of radiation was received occupationally by the father before the conception of each of the affected individuals. Forty-one cases of leukaemia and non-Hodgkin's lymphoma were diagnosed during 1968-85 in young people under 25 years of age resident in the 49 electoral wards lying within the boundary of West Cumbria and the adjacent ward of Broughton. Raised incidence rate ratios (two-sided P<0.01) were found for acute lymphoblastic leukaemia among those aged 0-14 years (concentrated among those aged 0-4 years) in Seascale ward and among those aged 0-24 years (also concentrated among those aged 0-4 years) in Egremont North ward, for acute myeloid leukaemia among those aged 0-14 years in Sandwith ward, for all leukaemias among those aged 0-14 years in Broughton ward (South Lakeland) and for non-Hodgkin's lymphoma among those aged 0-14 years in Seascale ward. For West Cumbria as a whole, incidence rates were not usual. Apart from Seascale, for none of these electoral wards has a father of an affected child been linked definitely to an occupational dose of radiation recorded before the conception of the child. Particularly striking are the excesses of acute lymphoblastic leukaemia cases among young children living in the wards of Seascale and Egremont North, situated 11 km apart. The cases in Egremont North are not associated with recorded doses of radiation received occupationally by fathers before the conception of the affected children, even though the total numbers of children associated with such doses born in Seascale and Egremont North wards are similar. This finding is further evidence against a causal role for paternal preconceptional radiation exposure in the cases of childhood leukaemia in Seascale.
STUDY OBJECTIVE: To investigate whether the occupational exposure to external ionising radiation of men employed at the Sellafield nuclear installation, West Cumbria, affects the sex of the children they subsequently father. DESIGN: A retrospective cohort study using logistic regression to analyse the sex ratio, in particular in relation to paternal preconceptional irradiation. SETTING AND PARTICIPANTS: The 260,060 singleton births between 1950 and 1989 to mothers resident in Cumbria, north west England. RESULTS: The sex ratio among children of men employed at any time at Sellafield was 1.094 (95% CI: 1.060, 1.128), significantly higher than that among other Cumbrian children, 1.055 (95% CI: 1.046, 1.063). There was an increased sex ratio of 1.396 (95% CI: 1.127, 1.729) in the 345 children whose fathers were estimated from annual dose summaries to have received more than 10 mSv of external radiation in the 90 days preceding conception, but no significant linear trend between sex ratio and 90 day paternal preconceptional dose was found. There was no significant association between sex ratio and the external dose accumulated before the 90 day period preceding conception. CONCLUSIONS: Men employed at Sellafield fathered a greater proportion of boys than would be expected for a Cumbrian population, which may be partly explained by their younger age distribution. A greater effect was observed in the fathers with recorded doses exceeding 10 mSv in the 90 days before conception. While this may reflect a true statistical association, it is also possible that it may be a chance finding due to imprecision in the dose estimates and consequent misclassification.
Workers employed in the nuclear energy industry and members of the general public living near nuclear facilities are exposed to low levels of ionising radiation as a result of the routine operation of these facilities. For the purposes of radiological protection, it is assumed that low doses of radiation confer a small increased risk of cancer upon the exposed individual and this is a major consideration in setting dose limits for workers and the general public. Quantitative estimates of radiation risk have been derived from epidemiological studies of groups exposed, on average, to high or moderate doses of radiation (such as the Japanese atomic bomb survivors), and appropriate assumptions are made for the application of such estimates to low dose conditions. There have been claims that the risks of cancer in nuclear industry workers, in their children, and in populations living around nuclear facilities have been grossly underestimated. Substantial evidence is now available from the epidemiological study of these groups. Studies of nuclear industry workforces demonstrate that currently accepted risk estimates are at about the right level, although a positive trend of leukaemia mortality with radiation dose, of a magnitude which is compatible with predictions, can be detected in the most statistically powerful workforce studies. The hypothesis that irradiation of fathers before the conception of their children materially increases the risk of childhood leukaemia has been largely discounted since it is biologically implausible and has found no support in studies using data independent of the study which generated the hypothesis. Increased levels of childhood leukaemia have occurred near certain nuclear facilities in the United Kingdom, but it is most unlikely that these are related to exposure to ionising radiation. Recent evidence suggests that these excesses are caused by a rare response to an infectious agent, which is enhanced under the unusual conditions of population mixing found in these communities. Similar excesses of childhood leukaemia have been found in other communities which have experienced unusual population mixing, but are not near nuclear facilities.
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Unless examiners are carefully selected, trained, and monitored, examinations may become haphazard. This is perhaps most true of oral or viva voce ("viva") examinations, which can generate marks unrelated to competence. To help other bodies to short circuit some years of experiment in connection with the oral component of the Royal College of General Practitioners' membership examination (MRCGP), this paper describes the selection, training, guidance, and monitoring arrangements that have been developed.
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The apparent risk of childhood leukemia resulting from paternal pre-conception radiation exposure found among children of the Sellafield (West Cumbria, UK) workforce is compared with the apparent risk in a number of other epidemiological studies. In particular, the extent of the incompatibility of the leukemia pre-conception exposure risks in the offspring of the Sellafield workforce born in the village of Seascale with the risks for those born in the rest of west Cumbria, and with the risks in the offspring of the Japanese bomb survivors, the Ontario radiation workers, and the Scottish radiation workers is discussed. A variety of animal data relating to the possibility of leukemia arising as a result of parental pre-conception exposure is also considered. It is concluded that the extent of the inconsistency of the leukemia risks in the Seascale data with this body of epidemiological and experimental data makes it highly unlikely that the association observed in the West Cumbria dataset represents a causal relationship.
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The findings of studies investigating whether exposures to ionizing radiation before birth, either pre- or post-conception, increase the risk of childhood cancer have provoked much scientific controversy. An epidemiological association between the abdominal exposure of pregnant women to diagnostic X-rays and childhood cancer was first reported in the 1950s, while an association between the recorded dose of radiation received occupationally by fathers before the conception of their offspring and childhood leukemia was reported only recently in 1990. The scientific interpretation of these particular statistical associations is by no means straightforward, but the latest analyses of intrauterine irradiation and childhood cancer indicate that a causal inference is likely. Scientific committees have adopted risk coefficients for the intrauterine exposure of somatic tissues, which for childhood leukemia are comparable to those accepted for exposure in infancy, although questions remain about the level of risk of childhood solid tumors imparted by exposure to radiation in utero and shortly after birth. In contrast, the association between paternal preconceptional radiation dose and childhood leukemia has not been confirmed by studies using objectively determined doses. The original association has been found to be restricted to children born in one village, it does not extend to cancers other than leukemia, and it is markedly inconsistent with the established body of knowledge on radiation-induced hereditary disease. A causal interpretation of this association has effectively been abandoned by scientific authorities.
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OBJECTIVE: To examine whether the geographical distribution of births associated with preconceptional exposure of fathers to radiation at the Sellafield nuclear installation is consistent with the suggestion that this exposure explains the excess of childhood lymphoid malignancy in the adjacent village of Seascale. DESIGN: Retrospective birth cohort study. SETTING: Cumbria, West Cumbria health district, and Seascale civil parish. SUBJECTS: The 10,363 children born in Cumbria during 1950-89 to fathers employed at Sellafield. MAIN OUTCOME MEASURES: The doses of external whole body ionising radiation received by fathers at Sellafield in the total time and in the six months before conception of their children; the proportions of the collective doses associated with Seascale and the rest of West Cumbria. RESULTS: 9256 children were born to fathers who had been exposed to radiation before the child's conception. Of these, 7318 had fathers who were exposed in the six months before conception. Overall 7% (38 person-Sv) of the collective total preconceptional dose and 7% (3 person-Sv) of the collective dose for the six months before conception were associated with children born in Seascale. Of all the children whose fathers worked at Sellafield, 842 (8%) were born in Seascale. The mean individual doses before conception were consistently lower in Seascale than in the rest of West Cumbria. CONCLUSIONS: The distribution of the paternal preconceptional radiation dose is statistically incompatible with this exposure providing a causal explanation for the cluster of childhood leukaemias in Seascale.
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