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Biomedical subjects

G W Kneale

Publications and source records attributed to G W Kneale.

At least 19 recordsLinked to original sources
PubMed2000

A-bomb survivors: factors that may lead to a re-assessment of the radiation hazard.

BACKGROUND: The study cohort of the survivors of the A-bombs in Japan, used as the basis of the internationally accepted estimates of cancer radiation risk, was collected more than 5 years after the bombing and did not include those who died of bomb-related injuries before that date. This paper tests whether the people who survived, in spite of bomb-related injuries, are homogeneous in respect of variation of cancer risk with age with survivors without such injuries. METHODS: Appropriate statistical models are derived and fitted to survivor data by maximum likelihood and the resultant statistics used to test the homogeneity assumption. RESULTS: Significant differences were found between those with no injuries and those with multiple injuries and shown to be largely due to exposures before 10 or after 55 years of age having exceptionally high risks of late effects of radiation for survivors showing early effects, i.e. bomb-related injuries. CONCLUSIONS: Certain accepted dogmas about the biology of radiation risks in humans, such as 'cancer is the only late effect of radiation' and 'leukaemia is uniquely radiogenic amongst cancers', may be significantly in error. These are discussed.

Adolescent↗
PubMed1997

Cancer in the offspring of radiation workers: a record linkage study.

OBJECTIVES: To test the "Gardner hypothesis" that childhood leukaemia and non-Hodgkin lymphoma can be caused by fathers' exposure to ionising radiation before the conception of the child, and, more generally, to investigate whether such radiation exposure of either parent is a cause of childhood cancer. DESIGN: Case-control study. SETTING: Great Britain. SUBJECTS: 35,949 children diagnosed as having cancer, together with matched controls. MAIN OUTCOME MEASURES: Parental employment as radiation worker as defined by inclusion in the National Registry for Radiation Workers and being monitored for external radiation before conception of child; cumulative dose of external ionising radiation for various periods of employment before conception; dose during pregnancy. RESULTS: After cases studied by Gardner and colleagues were excluded, fathers of children with leukaemia or non-Hodgkin lymphoma were significantly more likely than fathers of controls to have been radiation workers (relative risk 1.77, 95% confidence interval 1.05 to 3.03) but there was no dose-response relation for any of the exposure periods studied; indeed, the association was greatest for those with doses below the level of detection. No increased risk was found for fathers with a lifetime preconception dose of 100 mSv or more, or with a dose in the 6 months before conception of 10 mSv or more. There was no increased risk for the group of other childhood cancers. Mothers' radiation work was associated with a significant increase of childhood cancer (relative risk 5.00, 1.42 to 26.94; based on 15 cases and 3 controls). Only four of the case mothers and no controls were radiation workers during pregnancy. CONCLUSIONS: These results do not support the hypothesis that paternal preconception irradiation is a cause of childhood leukaemia and non-Hodgkin lymphoma; the observed associations may be chance findings or results from exposure to infective or other agents. If there is any increased risk for the children of fathers who are radiation workers, it is small in absolute terms: in Britain the average risk by age 15 years is 6.5 per 10,000; our best estimate, using all available data, is that the increase is 5.4 per 10,000. For mothers, the numbers are too small for reliable estimates of the risk, if any, to be made.

Adolescent↗
PubMed1996

Relations between age at occupational exposure to ionising radiation and cancer risk.

OBJECTIVES: To discover how the age when a given dose of ionising radiation is received (exposure age) affects the subsequent cancer risk, and whether the types of cancer caused by repeated exposure to small doses during adult life differ from naturally occurring cancers at that age. METHOD: A nested case-control design with all possible controls in a cohort of nuclear workers, and a Mantel-Haenszel test (requiring only one degree of freedom) to discover whether there was any level of exposure age where the null hypothesis of no effects of radiation was rejected. This analysis was followed by inspection of how different types of cancers were related to the cancer risk. RESULTS: For radiation received at least 15 years before a cancer death (to allow for cancer latency) evidence of a dose related risk was found which was largely the result of exposures during the last 10 years of working life (between 55 and 65 years of age). The relative frequency of site specific cancers showed no signs of being different for radiogenic and idiopathic cancers, and there was no evidence of the exceptionally strong association between radiation and leukaemia found in atomic bomb data and other high dose situations. CONCLUSIONS: Sensitivity to carcinogenic effects of radiation increases progressively with age during adult life and, provided the dose is too small to produce many cell deaths, the ratio of leukaemias to solid tumours is no different for radiogenic and idiopathic cancers.

Adult↗
PubMed1995

Factors affecting recognition of cancer risks of nuclear workers.

OBJECTIVES: To discover whether direct estimates of the risks of cancer for nuclear workers agree with indirect estimates based on survivors of the atomic bomb; whether relations between age at exposure and risk of cancer are the same for workers and survivors, and whether dosimetry standards are sufficiently uniform to allow pooling of data from different nuclear industrial sites. METHOD: Data from five nuclear sites in the United States were included in a cohort analysis that as well as controlling for all the usual factors also allowed for possible effects of three cancer modulating factors (exposure age, cancer latency, and year of exposure). This analysis was first applied to three distinct cohorts, and then to two sets of pooled data. RESULTS: From each study cohort there was evidence of a risk of cancer related to dose, and evidence that the extra radiogenic cancers had the same overall histological manifestations as naturally occurring cancers and were largely the result of exposures after 50 years of age causing deaths after 70 years. There were, however, significant differences between the five sets of risk estimates. CONCLUSIONS: Although the risks of cancer in nuclear workers were appreciably higher than estimates based on the cancer experiences of survivors of the atomic bomb, some uncertainties remained as there were non-uniform standards of dosimetry in the nuclear sites. The differences between nuclear workers and survivors of the atomic bomb were largely the result of relations between age at exposure and risk of cancer being totally different for workers and survivors and, in the occupational data, there were no signs of the special risks of leukaemia found in atomic bomb data and other studies of effects of high doses.

Adult↗
PubMed1993

Reanalysis of Hanford data: 1944-1986 deaths.

Reanalysis of Hanford data by a method, which is new only in the sense that it makes new uses of standard epidemiological procedures, has produced evidence of a cancer risk at low dose levels. By a conservative estimate, about three per cent of the pre-1987 cancer deaths of Hanford workers had occupational exposures to external radiation as the critical (induction) event. These radiogenic cancers were evenly distributed between five diagnostic groups, but as a result of there being much greater sensitivity to "cancer induction by radiation" after, rather than before, 50 years of age, they were concentrated among the cancers which proved fatal after 70 years of age. The reanalysis provides no support for the idea that radiation is more likely to cause leukemia than solid tumors, or the idea that there is reduced cancer effectiveness of radiation at low dose levels (dose rate effectiveness factor or DREF hypothesis), but the estimated proportion of radiogenic cancers was much higher for the 175 nonfatal cancers (which had other certified causes of death) than for the 1,732 fatal cases. Finally, according to the latest publication of the US Committee on Biological Effects of Ionizing Radiation (BEIR V), dose rate is more important than exposure age, and even a single exposure to 10 rem would only increase the normal cancer risk by four percent. Nevertheless, for all recorded exposures of Hanford workers, the estimated doubling dose was close to 26 rem; for exposures after 58 years, it was close to 5 rem, and for exposures after 62 years, it was less than 1 rem.

Age Factors↗
PubMed1993

A-bomb survivors: further evidence of late effects of early deaths.

Reanalysis of A-bomb survivor data has shown the following: a) in the high-dose (> 1 Gy) subgroups of the life span study cohort of 5-y survivors, there is a significant deficit of individuals who were < 10 y or > 50 y at the time of the bomb; and b) in the cohort on in utero children, there is a significant deficit of individuals who were < 8 wk of fetal age when exposed. This paper discusses how this selection bias has affected the perception of three effects of A-bomb radiation: marrow damage, carcinogenesis, and second-generation effects.

Age Factors↗
PubMed1990

A-bomb radiation and evidence of late effects other than cancer.

Cancer risk coefficients for ionizing radiation are currently based on the assumption that, after the bombing of Hiroshima and Nagasaki, there were no late effects of early selection (survival of the fittest) or acute marrow damage. These negative findings were the result of applying a linear model of relative risk to the deaths of 5-y survivors. By applying a linear-quadratic model to these deaths (i.e., a model with more than one degree of freedom), we have obtained evidence of longstanding competition between selection effects of the early deaths and other radiation effects, and also evidence that late effects of radiation include marrow damage as well as cancer. Consequently, the present method of risk estimation--by linear extrapolation of high dose effects--should no longer be used for estimating the cancer effects of occupational exposures or background radiation.

Humans↗
PubMed1989

Childhood cancers and their association with pregnancy drugs and illnesses.

In a case/control study of 8059 matched pairs, the effect of maternal exposure to drugs and illnesses during pregnancy on the relative risk (RR) of cancer in the child was investigated using conditional logistic regression techniques. Acute respiratory infections, particularly viral infections such as influenza, were associated with a significantly increased RR of all childhood cancers and of neoplasms of the reticulo-endothelial system (RES) in particular, (RR = 1.69 all cancers, RR = 1.81 RES neoplasms, RR = 1.59 solid cancers). An analysis of illnesses according to their physiological effects yielded a significant association between childhood leukaemia and febrile illnesses (RR = 1.27 RES neoplasms). A significant increase in RR was associated with maternal history of epilepsy (RR = 1.31 all cancers) rather than with exposure to anticonvulsant drugs. Vaccines showed a pattern of RR similar to that of acute viral infections. Consumption of antipyretics and analgesics significantly increased the RR of childhood cancer (RR = 1.36 all cancers). An analysis of drugs according to their metabolic reactions yielded a significant association between those undergoing amino acid conjugation (predominantly antipyretics and analgesics) and childhood cancer risk (RR = 1.76 solid cancers).

Female↗
PubMed1987

Ten-day rule.

Explore the source record for details and available documents.

Child↗
PubMed1986

Immunizations against infectious diseases and childhood cancers.

A study based upon an unusually large series of childhood cancers and matched controls found a significant deficit of case/control pairs in which the cancer case had fewer immunizations against infectious diseases than the matched control. All types of immunizations and cancers were affected but the case/control differences were more pronounced for older cases with late immunizations than for younger cases with early immunizations, and more pronounced for solid tumours than leukaemia. Therefore there may be immune system responses to immunizations (or simulated infections) which make it difficult for small clones of cancer cells to enlarge and are more successful in preventing localised tumours in adolescents than childhood leukaemias.

Adolescent↗