Problems And Paradigms: Ionising radiations from nuclear establishments and childhood leukaemias – an enigma

Evans, H. J.

doi:10.1002/bies.950121108

Cited by 15 publications

(7 citation statements)

References 55 publications

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“…This preconceptional irradiation (PPI) hypothesis suggested a new mechanism of leukaemogenesis in humans, and was highly controversial, as there was little evidence from other sources to suggest that childhood leukaemia could be caused by germline mutation. Moreover, fathers' radiation exposure was considered to be insufficient to cause the mutation rate required for the number of cases observed (Evans, 1990;Doll et al, 1994;Wakeford et al, 1994). Additionally, there was no evidence of a germline effect among the children of Japanese atomic bomb survivors (Kodaira et al, 1995(Kodaira et al, , 2004Izumi et al, 2003).…”

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confidence: 99%

New germline mutations in the hypervariable minisatellite CEB1 in the parents of children with leukaemia

et al. 2007

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Gardner and co-workers advanced the hypothesis that the Seascale leukaemia cluster could have been caused by new mutations in germ cells, induced by paternal preconceptional irradiation (PPI) exposure at the Sellafield nuclear installation. Since evidence has shown that PPI can increase the de novo germline mutation rate in hypervariable minisatellite loci, we investigated the hypothesis that sporadic childhood leukaemia might be associated with an increased parental germline minisatellite mutation rate. To test this hypothesis, we compared de novo germline mutation rates in the hypervariable minisatellite locus, CEB1, in family trios (both parents and their child) of children with leukaemia (n ¼ 135) compared with unaffected control families (n ¼ 124). The majority of case and control germline mutations were paternal (94%); the mean paternal germline mutation rates of children with leukaemia (0.083) and control children (0.156) were not significantly different (odds ratio, 95% confidence interval: 0.50, 0.23 -1.08; P ¼ 0.11). There were no significant differences in case and control parental allele sizes, case and control germline mutation progenitor allele sizes (2.74 vs 2.54 kb; P ¼ 0.56), case and control mutant allele sizes (2.71 vs 2.67 kb; P ¼ 0.90), mutant allele size changes (0.13 vs 0.26 kb; P ¼ 0.10), or mutational spectra. Within the limitation of the number of families available for study, we conclude that childhood leukaemia is unlikely to be associated with increased germline minisatellite instability.

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confidence: 99%

New germline mutations in the hypervariable minisatellite CEB1 in the parents of children with leukaemia

et al. 2007

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“…As a consequence, the report in 1990 by colleagues (1990a, 1990b) of the initial results of the West Cumbria leukaemia and lymphoma case-control study, showing statistically significant associations between leukaemia, or leukaemia and non-Hodgkin's lymphoma (NHL), in young persons (under 25 years of age) and doses of radiation recorded by film badges worn by fathers employed at the Sellafield nuclear installation before the conception of their children, generated considerable debate within the scientific community. The possibility of there being a causal connection between paternal preconception irradiation (PPI) and leukaemia in offspring, of the magnitude suggested by this study, was met with some scepticism (Abrahamson 1990, Evans 1990, Narod 1990, Baverstock 1991, Neel 1991, Sankaranarayanan 1992. Suggestions were made (Beral 1990, Gardner et al 1990b that the discrepancy between the leukaemia PPI risks in the West Cumbria study and those observed in the main human F 1 (first generation offspring) dataset (Yoshimoto et al 1990) might be related to the presence of internally deposited radionuclides in the Sellafield workforce, and in particular the alpha-particle emitting radioisotopes of plutonium, the organ doses from which were not taken into account in the West Cumbria study (Gardner et al 1990b).…”

Section: Introductionmentioning

confidence: 81%

A comparison of the risks of leukaemia and non-Hodgkin's lymphoma in the first generation offspring of the Danish Thorotrast patients with those observed in other studies of parental pre-conception irradiation

Little¹,

Wakeford

Charles

et al. 1996

J. Radiol. Prot.

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The high doses of alpha-particle radiation which Thorotrast delivers to the testes makes the study of offspring of patients, who were administered this diagnostic contrast medium, particularly relevant to the controversy regarding childhood leukaemia in the offspring of the male Sellafield workforce, as it has been suggested that the alpha-particle dose from actinides may, in part, account for the observed association between paternal pre-conception external irradiation and leukaemia. The risks of childhood leukaemia and non-Hodgkin's lymphoma found among the offspring of the male Danish cohort of neurosurgical patients injected with Thorotrast for cerebral arteriography are compared with those observed in the offspring of the Sellafield (western Cumbria), Ontario and Scottish radiation workers and in the offspring of the Japanese atomic bomb survivors. Risks are compared using linear and exponential forms of a relative risk model. The pre-conception exposure risks of leukaemia, or of leukaemia and non-Hodgkin's lymphoma, in the Danish study are statistically incompatible with the corresponding risks in the children of the Sellafield workforce ( P < 0.01), which is entirely due to incompatibility with the risks in the children of the Sellafield workforce born in Seascale ( P < 0.01). Indeed no cases arose in the Danish study. The statistical incompatibility between the offspring of the Danish patients and the Seascale-born offspring of the Sellafield workforce is independent of the models used and is insensitive to uncertainties in the gonadal dose estimates in the respective datasets or to uncertainties in the estimates of the background cancer rates in the Seascale and Danish populations. The risks of leukaemia and non-Hodgkin's lymphoma in the Danish dataset are statistically compatible with the risks observed in the offspring of the Sellafield workforce born elsewhere in western Cumbria and with those seen among the offspring of the Ontario or Scottish radiation workforces as well as with those in the offspring of the Japanese atomic bomb survivors. The statistical compatibilities of the leukaemia pre-conception exposure risks in these various groups are also independent of the models used. It is most unlikely that the Seascale childhood leukaemia cases are caused by paternal exposures to alpha-particle emitters such as plutonium. In each non-Seascale dataset the risks are consistent with there being no excess hazard of leukaemia associated with paternal pre-conception exposure to ionising radiation, and it would seem that the association seen for Seascale-born children should be attributed to chance.

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“…The findings remain controversial [Beral, 1990;Evans, 1990;MacMahon, 1992;Doll et al, 19941. The results have been questioned on several grounds, including lack of consistency with the Japanese atomic bomb results, other studies of cancer in children of nuclear plant workers that did not find any association, the lack of an increase in genetic diseases or birth defects in the Sellafield area, or the contention that the association was due to other exposures such as viruses.…”

Section: Atomic Bomb Survivorsmentioning

confidence: 99%

Lessons learned from epidemiologic studies of environmental exposure and genetic disease

Olshan

1995

Environ. Mol. Mutagen.

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The induction of germ cell mutations with ionizing radiation and chemicals has been clearly demonstrated in experimental animal test systems. Less is known about the effects of environmental and other exposures on human germ cells. Epidemiologic studies of atomic bomb and childhood cancer survivors and their offspring have generally not indicated an excess risk for a variety of adverse reproductive outcomes and childhood diseases, including those due to germ cell mutations. Other epidemiologic studies, including the investigation of cancer among the offspring of fathers employed at the Sellafield nuclear facility in Great Britain and studies of paternal occupation and birth defects, have found associations. This paper reviews these studies and the methodologic problems inherent in the epidemiologic approach to evaluating environmentally induced germ cell mutagenesis in humans. Epidemiologic studies incorporating newly developed techniques for the detection of mutations and abnormalities in sperm may provide the sensitivity needed to determine precisely the magnitude of risk.

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Problems And Paradigms: Ionising radiations from nuclear establishments and childhood leukaemias – an enigma

Cited by 15 publications

References 55 publications

New germline mutations in the hypervariable minisatellite CEB1 in the parents of children with leukaemia

New germline mutations in the hypervariable minisatellite CEB1 in the parents of children with leukaemia

A comparison of the risks of leukaemia and non-Hodgkin's lymphoma in the first generation offspring of the Danish Thorotrast patients with those observed in other studies of parental pre-conception irradiation

Lessons learned from epidemiologic studies of environmental exposure and genetic disease

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