Prognostic significance of Epstein-Barr virus association in Hodgkin's disease.
Explore the source record for details and available documents.
Disease-Free Survival↗
Biomedical subjects
F E Alexander
Publications and source records attributed to F E Alexander.
The Edinburgh randomised trial of breast cancer screening: results after 10 years of follow-up.
The Edinburgh Randomised Trial of Breast Cancer Screening recruited 44,288 women aged 45-64 years into the initial cohort of the trial during 1978-81, and 10 years of follow-up is now complete. A total of 22,944 women were randomised into the study group and were offered screening for 7 years; the remaining women formed the control group. After 10 years, breast cancer mortality is 14-21% lower in the study group than in the controls depending on the precise definition of the end point. These differences are not statistically significant; for breast cancer as the underlying cause of death the relative risk is 0.82 (95% confidence interval 0.61-1.11). Rates of locally advanced and metastatic cancer were substantially lower in the study group, but screening has failed to achieve marked reductions in rates of small node-positive cancers. Those women who accepted the final invitation to screening have been monitored over the 3 year period prior to their first screen under the UK service screening programme. Interval cases, expressed as a proportion of the control incidence, increased from 12% in the first year to 67% in the third year. The reduction in breast cancer mortality for older women (aged at least 50 years) is the same as that for the total study group for this duration of follow-up. For analyses of breast cancer mortality in younger women updates recruited to the trial from 1982 to 1985 (10,383 women with 6-8 years' follow-up) have been included. The reduction in breast cancer mortality for women aged 45-49 years at entry was 22% (relative risk = 0.78, 95% confidence interval = 0.46-1.31).
Breast Neoplasms↗
Epidemiological characteristics of childhood acute lymphocytic leukemia.
Explore the source record for details and available documents.
Child↗
Screening for breast cancer in the under 50s.
Explore the source record for details and available documents.
Adult↗
Viruses, clusters and clustering of childhood leukaemia: a new perspective?
Clusters of childhood leukaemia have, during a lengthy and controversial history, focussed attention on two alternative putative aetiological agents: infections and localised environmental pollution. In the United Kingdom emphasis is currently placed on the latter because of reports of localised clusters in the vicinity of two nuclear reprocessing plants. Now the most recent studies of spatial clustering in the United Kingdom also support the hypothesis that a substantial population of cases of childhood acute lymphoblastic leukaemia (ALL) arise as a rare host response to certain patterns of exposure to common infectious agents--the aberrant response model. Relevant aspects of the epidemiology of ALL are reviewed from this perspective and the hypothesis shown to be capable of unifying reported associations with different types of risk factor. It is probable that specific agent(s) are involved though none have been identified and these may share many epidemiological characteristics of herpes viruses. The possible relevance of these results to associations with prenatal parental occupational exposures to dusts and ionising radiation is explored.
Adolescent↗
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)
Adolescent↗
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.
Adolescent↗
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.
Adolescent↗
An infectious etiology for common acute lymphoblastic leukemia in childhood?
Childhood leukemia is a biologically and clinically diverse disease and is likely to arise via a number of etiological pathways. The common, B-cell precursor, form of acute lymphoblastic leukemia (cALL) accounts for the peak of childhood leukemia at 2-5 years of age. Recent epidemiological data, reviewed here, indicate that risk of cALL is increased by higher socio-economic status, isolation, and other community characteristics suggestive of abnormal patterns of infection during infancy. These data are compatible with the emerging concept that cALL may be a rare response to common infection(s).
Child↗
Paternal occupations of children with leukemia.
Explore the source record for details and available documents.
Child↗
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.
Case-Control Studies↗
Space-time clustering of childhood acute lymphoblastic leukaemia: indirect evidence for a transmissible agent.
Despite numerous anecdotal reports of small clusters of cases of childhood leukaemia, formal statistical analyses have yielded equivocal results (Linet, 1985). Incidence data from the UK national children's tumour registry (CCRG) for 1968-1983 have recently become available for small area analyses by location at diagnosis (OPCS, 1991). Extensive analyses using a variety of methodologies have shown consistent, though weak, evidence of the occurrence of both spatial clustering and space-time interactions. Results from one of these analyses (Alexander, 1991) are now extended to test specific prior hypotheses generated by an independent case-control study (Alexander et. al., 1992). These suggested that transmission of a specific, though unknown, agent (Z) plays some role in the development of childhood acute lymphoblastic leukaemia (ALL) with the times when children are susceptible to infection differing by age-of-onset and hence subtype of ALL. For cases with older onset (aged 5 years and over) it was suggested that persistent infection may have been established in utero or early infancy and, now, formal testing of appropriate space-time interactions provide indirect confirmation of this (P = 0.0002). More recent exposure to Z may contribute to ALL in the childhood peak years (Alexander et. al., 1992) but the confirmation provided here is less strong (P = 0.05). The results afford new impetus to a search for a transmissible aetiologic agent or agents; these need not be rare and the results should not be interpreted as evidence for direct case to case transmission.
Case-Control Studies↗
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.
Adult↗
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.
Adolescent↗
Community lifestyle characteristics and lymphoid malignancies in young people in the UK.
Data from a specialist registry of haematopoietic malignancies in England and Wales (1984-1988) have been analysed to investigate variations of incidence by age and diagnostic subtype of lymphoid malignancies in young people (aged 0-24 years). Attention has been focussed on the role of community lifestyle indicators for small areas, derived from routine sources, in an ecological analysis. The predominant conditions were acute lymphoblastic leukaemia (ALL)--42.4%, and Hodgkin's disease (HD)--37.5%. Lowest overall incidence at approximately 8 years of age corresponded to the termination of the childhood peak for ALL. Opposite trends of incidence rates with distance from urban centres (urban distance) were observed for the two age groups: odds ratios (OR) for areas greater than 20 km from towns and cities were 1.46 (95% confidence interval 1.01-2.12) for ages 0-7 and 0.75 (95% confidence interval 0.56-0.99) for ages 8-24. For the younger group this was entirely attributable to ALL. HD, which was dominant in the older group, had highest incidence in connurbations but the gradient of risk for older onset ALL followed the overall pattern for this age group. A positive relationship with socioeconomic status was evident for both age groups but this was considerably stronger for the older cases (OR = 1.16, 95% confidence interval 1.01-1.33) than for the younger for whom it was not independent of urban distance. These results display an association between expression of lymphoid malignancies in young people and urban distance which is not attributable to socioeconomic status; for urban distances the distribution is shifted towards ALL and towards younger age at onset.
Adolescent↗
Comparative pathology of breast cancer in a randomised trial of screening.
In the Edinburgh Randomised Breast Screening Project (EBSP) to December 1988 there were 500 cancers in the study population invited to screening and 340 cancers identified in the control population. The size and negative lymph node status characteristics of invasive cancers from the two populations were significantly different (P less than 0.05). The cancers detected by screening were predominantly 'early stage', with 16% noninvasive (PTIS) and 42% invasive stage I (pT1 node negative), whereas cancers were frequently 'late stage' (more than pT2) and inoperable in nonattenders (44%) and controls (36%). Grouped according to customary size ranges of invasive cancers, the proportion of cases lymph node positive differed in those screen detected compared with controls, but the benefit in favour of screen detection was not constant. In comparisons of cancers detected at prevalence and incidence screens, as a test of conformity with screening theory, no significant differences were apparent according to size and lymph node status, yet the characteristics of histological type of cancer discriminated significantly (P less than 0.05). When these same histological characteristics were used to compare survival, the capacity to separate invasive cancers into two groups having good and poor survival probabilities was evident, with a significant improvement for the screen detected poor survival group compared with controls (P less than 0.05).
Breast Neoplasms↗
Viral involvement in Hodgkin's disease: detection of clonal type A Epstein-Barr virus genomes in tumour samples.
Thirty-five cases of Hodgkin's disease (HD) were analysed for the presence of Epstein-Barr virus (EBV) and human herpesvirus-6 (HHV-6) DNA. EBV genomes were detected in 11/35 cases while none of the cases was positive for HHV-6. Ten of the EBV-positive cases were subsequently analysed using a probe for the terminal region of the virus; the results suggested that the EBV-infected cells were clonally expanded. EBV subtypes specific DNA amplification was used to demonstrate that EBV subtype A, and not subtype B was present in the EBV-positive cases. The age distribution of the EBV-positive cases indicated a statistically significant trend for an increase in positivity with increasing age. This is the first indication that EBV is significantly associated with any subset of HD patients.
Adolescent↗
Epidemiological evidence for the 'two-disease hypothesis' in Hodgkin's disease.
This study relates to 1803 newly diagnosed cases of Hodgkin's Disease (HD) registered between 1984 and 1988 by a specialist leukaemia-lymphoma registry covering approximately half of England and Wales. In addition to registration data the analyses use routine census data. Rye classification is available for the majority of cases with only 7% being unclassified. The data confirm that the young adult peak in HD occurrence is attributable to the nodular sclerosing subtype (NS), and there is some evidence that NS has a different geographical distribution by county to the other Rye subtypes. Because of possible geographical biases in the classification, subsequent spatial analyses are disaggregated by age at diagnosis with particular emphasis being placed on the two age groups 0-34 and 50-79 years. For these, trends of risk by areal socioeconomic status are in opposite directions and the effects of urban-rural status while in the same direction also differ significantly. Allowance for these does not, however, explain the significant difference between the county distributions of the two groups. Patterns of spatial clustering are quite distinct with evidence for local spatial aggregation amongst younger cases.
Adolescent↗