Biomedical subjects
L J Kinlen
Publications and source records attributed to L J Kinlen.
Paternal occupational contact level and childhood leukaemia in rural Scotland: a case-control study.
In a national Scottish study of 809 cases of leukaemia and non-Hodgkins lymphoma diagnosed in 1950-89 among children aged 0-4 years who were born in Scotland, together with 2363 matched population controls, we investigated one aspect of the infective hypothesis. This concerns whether in rural areas (where the prevalence of susceptible individuals is likely to be higher) the risk is greater among the young children of men whose work involves contacts with many different people, particularly children, as noted in certain childhood infections. A positive trend was found in rural areas across 3 levels of increasing paternal occupational contact (as recorded at birth) by each of 2 previously defined classifications; no such effect was found in urban areas. The rural trend was more marked in that part of the study period with greater population mixing, but the difference from the period with less mixing was not itself significant, leaving open whether these rural findings reflect the extreme isolation of much of rural Scotland, or the effects in such areas of a degree of population mixing. In marked contrast, among the 850 cases and 2492 controls aged 5-14, those in rural areas in the higher population mixing period showed a significantly decreasing trend with increasing paternal occupational contact level. This would be consistent with immunity produced either by earlier infection at ages 0-4 years, or directly by low doses of the infective agent that were largely immunizing at these older ages. The findings overall provide further support for infection underlying childhood leukaemia and for the role of adults.
Infective cause of childhood leukaemia and wartime population mixing in Orkney and Shetland, UK.
In Orkney and Shetland (the UK's northernmost islands), during World War II, local people were outnumbered by servicemen stationed there in case of a northern invasion. Such rural-urban population mixing promotes contact between susceptible and infected individuals. We compared childhood leukaemia mortality in wartime and postwar cohorts of Orkney and Shetland children. Childhood leukaemia increased 3.6-fold, (p=0.001) in the wartime, but not in the postwar, cohort compared with national Scottish rates. These findings add to the evidence for infection as a cause of childhood leukaemia.
Non-Hodgkin's lymphoma after immunosuppressive therapy.
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Childhood leukaemia, population mixing, and paternal occupation.
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Risk of breast cancer and other cancers in heterozygotes for ataxia-telangiectasia.
Mortality from cancer among 178 parents and 236 grandparents of 95 British patients with ataxia-telangiectasia was examined. For neither parents nor grandparents was mortality from all causes or from cancer appreciably elevated over that of the national population. Among mothers, three deaths from breast cancer gave rise to a standardized mortality ratio of 3.37 (95% confidence interval (CI): 0.69-9.84). In contrast, there was no excess of breast cancer in grandmothers, the standardized mortality ratio being 0.89 (95% CI: 0.18-2.59), based on three deaths. This is the largest study of families of ataxia-telangiectasia patients conducted in Britain but, nonetheless, the study is small and CIs are wide. However, taken together with data from other countries, an increased risk of breast cancer among female heterozygotes is still apparent, though lower than previously thought.
Infection and childhood leukemia.
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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.
Infection and childhood leukaemia near nuclear sites.
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High-contact paternal occupations, infection and childhood leukaemia: five studies of unusual population-mixing of adults.
The hypothesis has been tested that, among excesses of childhood leukaemia associated with extreme population-mixing, the incidence is higher for the children of men in occupations involving contact with many individuals (particularly children), as noted in certain childhood infections. Data on childhood leukaemia were examined from five previous studies of the author in which significant excesses had been found associated with population-mixing involving adults. Occupational titles were categorized according to the estimated level of work contacts as medium, high, very high or indeterminate. Occupations involving frequent contact with children were categorized as having a very high contact level given the high frequency of exposure to the infection postulated as underlying childhood leukaemia. There was a significant positive trend (P < 0.001) in childhood leukaemia risk at ages 0-14 years across the occupational contact categories from the reference group (comprising the medium and low plus indeterminate categories) through high to very high (i.e. high-child) contact categories in the combined data from the author's five studies of adult population-mixing; this significant trend also applied at ages 0-4 (P < 0.001) and 5-14 (P < 0.01) years. The excess in the high category was mainly because of paternal occupations connected with the construction industry and transport, suggesting a broader definition of the 'very high' contact category. No sign of these excesses was found in a limited examination of the question outside areas of population-mixing using mortality data for childhood leukaemia in the general population of England and Wales. The findings represent the first individual-based support for infection underlying childhood leukaemia that is promoted by population-mixing, as well as further support for the role of adults in transmission of the infection.
Childhood leukaemia and non-Hodgkin's lymphoma near large rural construction sites, with a comparison with Sellafield nuclear site.
OBJECTIVE: To determine whether population mixing produced by large, non-nuclear construction projects in rural areas is associated with an increase in childhood leukaemia and non-Hodgkin's lymphoma. DESIGN: A study of the incidence of leukaemia and non-Hodgkin's lymphoma among children living near large construction projects in Britain since 1945, situated more than 20 km from a population centre, involving a workforce of more than 1000, and built over three or more calendar years. For periods before 1962 mortality was studied. SETTING: Areas within 10 km of relevant sites, and the highland counties of Scotland with many hydroelectric schemes. SUBJECTS: Children aged under 15. RESULTS: A 37% excess of leukaemia and non-Hodgkin's lymphoma at 0-14 years of age was recorded during construction and the following calendar year. The excesses were greater at times when construction workers and operating staff overlapped (72%), particularly in areas of relatively high social class. For several sites the excesses were similar to or greater than that near the nuclear site of Sellafield (67%), which is distinctive in its large workforce with many construction workers. Seascale, near Sellafield, with a ninefold increase had an unusually high proportion of residents in social class I. The only study parish of comparable social class also showed a significant excess, with a confidence interval that included the Seascale excess. CONCLUSION: The findings support the infection hypothesis and reinforce the view that the excess of childhood leukaemia and non-Hodgkin's lymphoma near Sellafield has a similar explanation.
Childhood leukemia and rural population movements: Greece, Italy, and other countries.
Mortality from childhood leukemia was examined particularly in rural countries in relation to any major rural-urban migration. Significant increases have been found in other situations of rural population mixing as predicted by the infection hypothesis. The 1950s and 1960s were of most interest since it preceded the decline in mortality brought about by effective chemotherapy in many countries. The 33 countries covered were all those in the World Health Organization's mortality database. No sensitive measure of rural-urban migration is available for international comparisons. However, it seems noteworthy that Greece and Italy, the two countries with the most striking levels of rural migration in the 1950s and 1960s, also had unusually high mortality rates from childhood leukemia. Greece was most affected proportionally by these population movements and from 1958 to 1972 had the highest recorded mortality from this cause in the world. The problems of international comparisons of mortality data dictate caution in drawing conclusions. However, against a background of other work on population mixing, and in the light of certain considerations, we suggest that the marked rural population mixing in Greece and Italy may have contributed to their high mortality rates from childhood leukemia in the 1950s and 1960s.
Epidemiological evidence for an infective basis in childhood leukaemia.
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Wartime evacuation and mortality from childhood leukaemia in England and Wales in 1945-9.
OBJECTIVE: To discover whether the wartime government evacuation of children from London and other population centres to rural districts was associated with any increase in childhood leukaemia. DESIGN: Observational study of mortality from leukaemia among the childhood population of England and Wales in relation to the unique population movements during the second world war. The 476 rural districts of England and Wales were ranked according to the ratio of government evacuees (two thirds of them children) to local children in September 1941. The districts were divided into three categories, each with similar numbers of children in 1947 but with different ratios of evacuees to local children ("low," "intermediate," "high"). Mortality from childhood leukaemia was examined in these three rural categories in 1945-9. Urban areas were also examined according to their exposure to evacuees. SETTING: Local authority areas of England and Wales. SUBJECTS: Children aged under 15. RESULTS: 47% excess of leukaemia at ages 0-14 years occurred in 1945-9 in the rural "high" category for evacuees relative to the "low" category, with a significant trend across the three categories. There were increases in both the 0-4 and 5-14 year age groups, but these were larger in the older age group. Rates 25% lower than average occurred in rural areas with few evacuees. CONCLUSION: These findings suggest that wartime evacuation increased the incidence of childhood leukaemia in rural areas and that other forms of population mixing may have contributed to the increases in past decades. Overall, they add to the appreciable evidence for an infective basis in childhood leukaemia.
Leukaemia mortality among young people in growing French communes.
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Leukaemia.
The most striking and consistent trend in leukaemia in different countries since 1950 is the recent decline in mortality in childhood, reflecting the advent of effective methods of treatment in the 1960s. Increases at ages 75-84 in several countries since 1950 are consistent with improvements in cancer registration and in the detail of death certification. However, in the main, these have not persisted into the 1980s. Otherwise, there has been no obvious international pattern, and partly for this reason, the rates have been presented in some detail so that readers can make their own judgment.
Can paternal preconceptional radiation account for the increase of leukaemia and non-Hodgkin's lymphoma in Seascale?
OBJECTIVE: To determine if the excess of leukaemia and non-Hodgkin's lymphoma in Seascale is restricted to those born in the parish and whether it might be explained by the postulated relation with paternal preconceptional radiation. DESIGN: Comparison, separately for those born in the parish and those born elsewhere, of the numbers of these malignancies observed in Seascale with those expected on the basis of reference rates for England and Wales. Details of paternal radiation levels were sought for each case. SETTING: The parish of Seascale in west Cumbria. SUBJECTS: Residents of Seascale below age 25 years in the years 1951-91. MAIN OUTCOME MEASURES: The observed and expected numbers of cases of leukaemia and non-Hodgkin's lymphoma within Seascale among those born there and among those born elsewhere. Also, the levels of any paternal preconceptional radiation associated with each case. RESULTS: A significant excess of leukaemia and non-Hodgkin's lymphoma at ages 0-24 was found in Seascale in those who were born there (ratio of observed to expected cases 8.6 and 20.2 respectively; p < 0.01). This also applied to those not born there (7.2 and 16.5; p < 0.01), a group often regarded as not showing an excess. The estimates were then conservatively recalculated so as to overestimate the risks among those born in Seascale and underestimate them among those born elsewhere. On this basis the six cases in those born in Seascale compare with 0.38 expected (15.8; p < 0.001), of which two were associated with paternal preconceptional life-time levels of 100 mSv or greater and three others with levels of 90-99 mSv. Among those born elsewhere, there were five cases (expected 0.74; ratio 6.7, p < 0.01), of which only one was associated with a high level of such radiation. CONCLUSIONS: Paternal preconceptional radiation cannot be the sole cause of the excess in Seascale since it will not explain the excess among those born outside Seascale. It follows that, unless two causes are to be postulated, any single cause must be a factor other than paternal preconceptional radiation. On this basis, the association found among those born there, if not partly due to chance, may reflect an indirect relation with the true cause. The recent hypothesis about such paternal radiation has originated in a subgroup of the excess cases that have aroused concern.