Biomedical subjects
R A Cartwright
Publications and source records attributed to R A Cartwright.
Cancer in Cumbria and in the vicinity of the Sellafield nuclear installation, 1963-90.
OBJECTIVE: To reappraise the epidemiological findings reported by the Black Advisory Group concerning a possible excess of malignant disease, particularly of childhood acute lymphoid leukaemia and non-Hodgkin lymphomas, in the vicinity of the Sellafield nuclear installation, and to determine whether any excess of malignant disease had occurred among people aged 0-24 years in the area in the years after the Black report--that is, from 1984 to 1990. DESIGN: Calculation of incidence of cancer using data from population based cancer registries and special surveys. SETTING: England and Wales; county of Cumbria; county districts Allerdale and Copeland within Cumbria; Seascale ward within Copeland. SUBJECTS: All residents under the age of 75 years in the above areas, but with particular reference to those aged 0-24 years. MAIN OUTCOME MEASURES: Numbers of cases and incidence particularly of lymphoid leukaemia and non-Hodgkin lymphomas in those aged 0-24 years, but including other cancers and age groups. RESULTS: Previous reports of an increased incidence of cancer, especially of leukaemia, among those aged 0-24 years in Seascale during the period up to and including 1983 are confirmed. During 1984-90 there was an excess of total cancer among those aged 0-24 years. This was based on four cases including two cases of non-Hodgkin lymphoma but none of leukaemia. There was an increased, but nonsignificant, incidence of other cancers, based on two cases (one pinealoma and one Hodgkin's disease) occurring among those aged 15-24 years during 1984-90. This was not observed in the younger age group or in previous years. For the immediately surrounding area--that is, the county districts of Allerdale and Copeland excluding Seascale and in the remainder of Cumbria--there was no evidence of an increased incidence of cancer among those aged 0-24 years in either period. CONCLUSIONS: During 1963-83 and 1984-90 the incidence of malignant disease, particularly lymphoid leukaemia and non-Hodgkin lymphomas, in young people aged 0-24 in Seascale was higher than would be expected on the basis of either national rates or those for the surrounding areas. Although this increased risk is unlikely to be due to chance, the reasons for it are still unknown.
The epidemiology of diabetes mellitus in the United Kingdom: the Yorkshire Regional Childhood Diabetes Register.
A register of the incidence of Type 1 (insulin-dependent) diabetes mellitus in the Yorkshire region of the United Kingdom has been completed. A total of 1,490 subjects aged between 0 and 16 years were identified from 1978 to 1990, giving an incidence of 13.7 per 100,000 (ages 0-14) or 13.6 per 100,000 (ages 0-16), comparable to other recent studies in the United Kingdom. An age-period-cohort analysis shows evidence for a modest drift effect of 1.75% per year (95% confidence interval 0.28 to 3.25%). There is a marked epidemic pattern with peaks at 4-year intervals. The age-incidence curve is similar to that reported elsewhere, having peaks in early childhood and puberty. Girls have an earlier pubertal peak than boys. There is substantial seasonal variation in incidence confined to those over 5 years of age. Ascertainment is believed to be very complete, and is estimated to be 97.6% (95% confidence interval 97.2% to 98.1%).
Congenital abnormalities in children with cancer and their relatives: results from a case-control study (IRESCC).
Several studies have revealed an excess of malformations in children with certain malignancies. A few environmental causes have been identified which may damage the foetus and lead to malformation and cancer. However, most of the numerous recognised cancer/malformation syndromes are genetically determined. This report describes a case-control study of 555 newly diagnosed children with cancer and 1,110 matched controls, chosen from general practitioner lists (GP controls) and hospital admissions (H controls). Their parents were interviewed on topics of possible aetiological significance and medical records were checked to confirm reports at interview. The numbers of congenital malformations in the index and GP control children, and the relatives of the index children, the GP and H controls are described. There were more children with malformations among the cases (60/555) than among the GP controls (27/555), P < 0.001. The abnormalities in the cases included eight with specific chromosomal/genetic conditions (e.g. Down's syndrome, XY gonadal dysgenesis, Von Recklinghausen's neurofibromatosis, Goldenhar's syndrome) whereas only one GP control child had a chromosomal defect (P < 0.05). Five case children but no GP controls had neural tube defects; this is not statistically significant. No excess of malformations was found in the siblings of cases compared with GP and H control siblings. Case mothers had a small excess of malformations (22/555) compared with GP controls (8/555), P < 0.05. Among more distant relatives the results were difficult to interpret because of the relatively small numbers in the diagnostic subgroups and because of apparent under reporting in grandparents, but no striking differences were seen between case and control relatives. The excess of malformations found in children with cancer, compared with controls, without a similar excess of malformations in their close relatives may indicate that in some (perhaps very roughly one in 20) cases antenatal events may lead both to the malformation and the malignancy.
Migration patterns of children with leukaemia and non-Hodgkin's lymphoma in three areas of northern England.
As part of a more comprehensive study, complete residential histories were collected from 109 cases of childhood leukaemia and non-Hodgkin's lymphoma who were diagnosed while resident in Gateshead, West Cumbria or North Humberside (1973-1987), and who were born in the same areas. Corresponding data were obtained from the same number of controls matched by date of birth, sex and area of residence at diagnosis and birth. Altogether, 1332 years of residential history were available for analysis and of these 131 (9.8 per cent) included a change of home. Moving house was much more frequent for both cases and controls in the first two years of life (69 out of 432 child-years, i.e. 16 per cent). The moves were mostly over short distances, with only 23 per cent being 5 km or more and only 9 per cent into another administrative district. Twenty-eight per cent of the children had moved house at least once by their second birthday and 48 per cent by the age of five years. Few case-control differences were apparent and none achieved statistical significance. There was a suggestion of more mobility for case children in the first few years of life, especially for cases diagnosed shortly after the removal. When the residence of mothers in the year preceding the childrens' birth was examined, there were relatively few removals in this period (26, i.e. 24 per cent, altogether, of which 14 were over 5 km and nine from another administrative district). Of these, 18 case mothers had moved (11 over 5 km) compared with eight control mothers (three over 5 km).(ABSTRACT TRUNCATED AT 250 WORDS)
Hairy cell leukaemia: descriptive epidemiology and a case-control study.
The descriptive epidemiology of hairy cell leukaemia is reported from a specialized register of haematological malignancies covering approximately one-third of England and Wales. The overall incidence of hairy cell leukaemia at 2.9 per million persons per year is similar to that recorded in America. There is a marked male preponderance (4.0 compared with 1.7 per million per year for females). A case-control study on hairy cell leukaemia was conducted in the Yorkshire and Trent Regional Health Authority areas. 50 cases and 95 controls were identified, and interviewed using a structured questionnaire. Previous results on the aetiology of hairy cell leukaemia were not supported by this study, with the exception of an association between hairy cell leukaemia and exposure to organic solvents, petrochemicals and related products.
Association of Epstein-Barr virus with pediatric Hodgkin's disease.
A bimodal age incidence curve has been shown for Hodgkin's disease (HD). In developing countries, the first age incidence peak occurs in childhood; however, this peak is delayed until young adulthood in developed countries. This difference may reflect differences in the age of exposure to infectious agents involved in the development of HD or may suggest different etiological agents. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a proportion of HD cases. In this study, EBV association was investigated in a series of 55 pediatric HD cases from three geographical locations (United Kingdom, Brazil, and Saudi Arabia) and the relationship between country, age, sex, histological subtype, and EBV positivity was evaluated. EBV was detected in 38 cases using RNA in situ hybridization, Southern blot, or immunohistochemical analysis. No significant difference in EBV positivity by country, age, or sex was observed; however, children under 10 years of age were particularly likely to be EBV-associated. The difference in EBV association in the pediatric group compared with that observed previously for young adult HD was highly statistically significant (P < 0.0001). These results are consistent with the hypothesis that pediatric and young adult HD have different etiologies and suggest that EBV is likely to be involved in the pathogenesis of pediatric HD.
Acute lymphoblastic leukaemia incidence in the UK by immunophenotype.
The incidence of acute lymphoblastic leukaemia (ALL) is described for both children and adults for the three major immunophenotypes: null, CD10-positive (CD+) which includes both common and pre-B types, and T-cell (including pre-T variants). The data are derived from a population-based specialist registry of leukaemias and lymphomas covering approximately one-half of England and Wales. Null ALL predominates in those under 1 year old and CD10+ ALL in the 1-7 year olds. There is a male excess at all ages for T-cell disease, which is particularly prominent in adolescents and young adults. The effect of socioeconomic levels is seen most clearly for CD10+ ALL in the childhood peak, where B-cell precursor disease occurs more frequently in areas of higher socioeconomic status.
Linkage analysis of early-onset breast and ovarian cancer families, with markers on the long arm of chromosome 17.
We have conducted linkage analysis in 16 breast cancer families, 13 of which are classified as site-specific breast cancer families and 3 of which are classified as breast-ovary families. Linkage analysis has largely focused on a single extended breast-ovary family. Analysis of all families combined shows significant evidence for linkage to 17q (LOD = 3.63 at theta = .0, for linkage to NME1), confirming the observations of Hall et al. and Narod et al. Many families were consistent with linkage, but their limited size and informativeness precluded confirmation of linkage. A putative recombinant in a breast-ovary family suggests that BRCA1 is distal to D17S250.
Changes in the descriptive epidemiology of non-Hodgkin's lymphoma in Great Britain?
The problems associated with a diagnosis of non-Hodgkin's lymphoma are reviewed in the context of an apparent rise in incidence. It is concluded that a true rise exists and that further work is required to fully understand the significance of this.
Paternal occupations of children with leukemia.
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Leukemia clusters around nuclear facilities in Britain.
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Leukaemia epidemiology and radiation risks.
This review deals with the associations between exposure to ionising and non-ionising irradiation and the risks of leukaemia. A systematic approach is adopted to enable the reader to disentangle the different types of exposure and their resultant effects (if any) on leukaemogenesis.
Residential proximity of children with leukaemia and non-Hodgkin's lymphoma in three areas of northern England.
A retrospective population-based case-control interview study has been conducted in three distinct areas in the north of England where local excesses of children with leukaemia have been reported. A total of 109 cases of childhood (0-14 years at diagnosis) leukaemia and non-Hodgkin's lymphoma who were born in one of the study areas and diagnosed there between 1974 and 1988 were included in the study. One control per case was matched on sex, date-of-birth and health district of birth. The objective was to compare residential histories of cases and controls and in particular to determine whether case children had lived in the same place at the same time more often than controls. The residential distance between two children was taken to be the smallest geographical distance between homes they had 'occupied' simultaneously for a period of at least 6 months between conception and diagnosis. Case children were more likely than expected to have other cases as their nearest neighbours by residential distance (observed = 69, expected = 54.5, P = 0.006). A detailed examination of the nearest neighbour pattern permits the generation of further specific hypotheses. These suggest that persistent infection established in utero or early infancy may be involved in the development of some cases of childhood leukaemia. Horizontal transmission of the agent(s) within small communities may occur but there is no evidence of direct contact between cases.
Childhood lymphoma in Yorkshire.
AIMS: A histopathological review of 43 cases of childhood non-Hodgkin's lymphoma (NHL) in an attempt to identify histological variables of prognostic importance. METHOD: Each case was reclassified according to the Working Formulation and an attempt made to allocate an immunophenotype using a panel of monoclonal antibodies. Results were correlated with clinical data on site and survival. RESULTS: Of the 43 cases, 30 were males and 13 females. There were 17 cases of lymphoblastic lymphoma, 15 cases of small non-cleaved cell lymphoma (SNCC), and four cases of large cell lymphoma. The SNCC group was subdivided into 10 cases of Burkitt's lymphoma and five cases of non-Burkitt's lymphoma. An immunophenotype was allocated in 65.1% of cases (23 B, 5 T). The SNCC cases were spread throughout the 0-16 year age range while the lymphoblastic lymphoma cases tended to occur in older children. Most mediastinal tumours were lymphoblastic lymphoma and most abdominal tumours were SNCC. Statistical analysis failed to show a significant difference in survival among histological subgroups or immunophenotypes. CONCLUSION: No histological variables of prognostic importance were identified partly due to the great variation in treatment regimens, standard of supportive care, and prognosis over the period of the study (1972 to 1988).
Community lifestyle characteristics and incidence of Hodgkin's disease in young people.
Risk of Hodgkin's disease (HD) in young adults has frequently been associated with limited access to social contact in childhood and related correlates of childhood social class. In addition, case clustering has sometimes been associated with influxes of population into relatively isolated communities. To investigate this further, disease incidence rates for HD at ages 0 to 24 from a specialist tumour registry have been regressed against relevant electoral ward characteristics derived from routine census and Ordnance Survey data for England and Wales. Proximity to built-up areas and higher socio-economic status (SES) emerge as significant risk factors. The relative risks are 1.21 (95% Cl: 1.01-1.46) for high SES wards and 1.29 (1.05-1.58) for "inner zone" wards. No association of disease risk with distance travelled to work was apparent. Regions farther from built-up areas have a lower overall incidence and a shift, particularly for males, of the age distribution towards older ages. The distribution resembles the intermediate pattern for HD reported from European rural areas of low SES but never previously for high SES. Isolated areas also show an increased intensity of spatial clustering (29% of cases being classified as clustered). These findings have implications for the 'late host response' model which suggest a viral aetiology for Hodgkin's disease in young people and provide a basis for future analytical studies.
Parental occupations of children with leukaemia in west Cumbria, north Humberside, and Gateshead.
OBJECTIVE: To determine whether parental occupations and chemical and other specific exposures are risk factors for childhood leukaemia. DESIGN: Case-control study. Information on parents was obtained by home interview. SETTING: Three areas in north England: Copeland and South Lakeland (west Cumbria); Kingston upon Hull, Beverley, East Yorkshire, and Holderness (north Humberside), and Gateshead. SUBJECTS: 109 children aged 0-14 born and diagnosed as having leukaemia or non-Hodgkin's lymphoma in study areas during 1974-88. Two controls matched for sex and date and district of birth were obtained for each child. MAIN OUTCOME MEASURES: Occupations of parents and specific exposure of parents before the children's conception, during gestation, and after birth. Other adults living with the children were included in the postnatal analysis. RESULTS: Few risk factors were identified for mothers, although preconceptional association with the food industry was significantly increased in case mothers (odds ratio 2.56; 95% confidence interval 1.32 to 5.00). Significant associations were found between childhood leukaemia and reported preconceptional exposure of fathers to wood dust (2.73, 1.44 to 5.16), radiation (3.23, 1.36 to 7.72), and benzene (5.81, 1.67 to 26.44); ionising radiation alone gave an odds ratio of 2.35 (0.92 to 6.22). Raised odds ratios were found for paternal exposure during gestation, but no independent postnatal effect was evident. CONCLUSION: These results should be interpreted cautiously because of the small numbers, overlap with another study, and multiple exposure of some parents. It is important to distinguish periods of parental exposures; identified risk factors were almost exclusively restricted to the time before the child's birth.