ABSTRACT
In this study, we have shown that there are seasonal differences in the onset of the (Epstein-Barr virus) EBV-positive and -negative forms of paediatric Hodgkin's lymphoma (HL). This suggests aetiological differences between the two forms of this disease. EBV-positive HL might be a rare consequence of primary EBV infection.
Subject(s)
Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/isolation & purification , Hodgkin Disease/virology , Seasons , Adolescent , Child , Child, Preschool , Epstein-Barr Virus Infections/epidemiology , Hodgkin Disease/epidemiology , Humans , Immunoenzyme Techniques , Infant , Infant, Newborn , Prevalence , United Kingdom/epidemiology , Viral Matrix Proteins/analysisABSTRACT
BACKGROUND: Conflicting data on the effect of the Epstein-Barr virus (EBV) on outcome in Hodgkin's disease (HD) might be due to the heterogeneous nature of this disease. In this study we have investigated whether the effect of EBV status on outcome is different between aetiologically defined age groups (15-34, 35-44, 45+ years) and also between males and females. PATIENTS AND METHODS: Paraffin-embedded sections from 273 patients with advanced HD from two related clinical trials were analysed for the presence of EBV using in situ hybridisation. RESULTS: EBV was detected in 78 (29%) of cases. For all patients, after a median follow-up of 5 years, there were no significant differences in survival by EBV status although there was a trend towards longer failure-free survival times for EBV-positive patients. Multivariate analyses suggested that EBV and sex, when in combination, were prognostic factors for failure-free survival (P = 0.06 for both). For subgroups, the effect of EBV on failure-free survival was significant for males and 15-34 years age group (P = 0.05 and P = 0.03, respectively). CONCLUSION: This study suggests that with a median follow-up of 5 years, EBV status does not affect survival but being EBV-positive may be beneficial in terms of failure-free survival, particularly for males and younger adults.
Subject(s)
Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human/pathogenicity , Hodgkin Disease/pathology , Hodgkin Disease/virology , Adolescent , Adult , Age Factors , Disease-Free Survival , Female , Humans , Male , Middle Aged , Sex FactorsABSTRACT
Epstein-Barr virus has been associated with a proportion of typical gastric adenocarcinomas. Here we report that the prevalence of Epstein-Barr virus in gastric adenocarcinomas from the United Kingdom is one of the lowest in the World. Gastric adenocarcinoma is another tumour whose association with Epstein-Barr virus varies with the population studied.
Subject(s)
Adenocarcinoma/etiology , Adenocarcinoma/virology , Epstein-Barr Virus Infections/complications , Stomach Neoplasms/etiology , Stomach Neoplasms/virology , Adenocarcinoma/epidemiology , Adult , Aged , Aged, 80 and over , Epidemiologic Studies , Epstein-Barr Virus Infections/epidemiology , Female , Humans , Male , Middle Aged , Prevalence , Stomach Neoplasms/epidemiology , United Kingdom/epidemiologyABSTRACT
In order to further define the factors associated with the observed variations in the Epstein-Barr virus-positive rate in childhood Hodgkin's disease, we have studied the effect of material deprivation (measured by the Townsend score) and ethnic origin on the frequency of Epstein-Barr virus-positivity in 55 cases of childhood Hodgkin's disease, diagnosed between 1981 and 1999, from a multi-ethnic region of the United Kingdom. Epstein-Barr virus status was determined by immunohistochemistry for the Epstein-Barr virus-encoded latent membrane protein-1. 62% of cases were Epstein-Barr virus-positive. Ethnic group was the strongest predictor of Epstein-Barr virus-positivity, with South Asians having a more than 20-fold risk of being Epstein-Barr virus-positive compared with non-South Asians. An increased risk was still present after adjusting for deprivation. Townsend scores were significantly higher (indicating more deprivation) in the Epstein-Barr virus-positive group, particularly in males. The relative risk of Epstein-Barr virus-positivity showed a gradient with increasing Townsend score; the risk being 7-times higher in the most deprived quartile compared with the least deprived group. Although the association between Townsend score and Epstein-Barr virus-positivity was reduced after adjusting for ethnic group, the risk of Epstein-Barr virus-positivity was still 3-times higher in the most deprived compared with the least deprived quartile. In addition, cases having 2 or more siblings were 5-times as likely to be Epstein-Barr virus-positive as those from smaller families. These results provide the first evidence of a strong association between Epstein-Barr virus-positive Hodgkin's disease and South Asian children from the United Kingdom. In addition, deprivation may increase the likelihood of Epstein-Barr virus-positive disease independently of ethnicity.
Subject(s)
Economics , Epstein-Barr Virus Infections/ethnology , Hodgkin Disease/ethnology , Adolescent , Adult , Antigens, Viral/immunology , Asia/epidemiology , Child , Child, Preschool , Epstein-Barr Virus Infections/virology , Female , Hodgkin Disease/virology , Humans , Immunohistochemistry , In Situ Hybridization , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Risk Factors , Viral Matrix Proteins/immunologyABSTRACT
Hodgkin's disease is an unusual cancer because the malignant cells constitute only a minority of the total tumour mass and, as a consequence, the study of these cells has been a major challenge. Recently, the application of newer technologies, such as single cell polymerase chain reaction (PCR) and gene expression array analysis, to the study of Hodgkin's disease have yielded new insights into the pathogenesis of this tumour. In addition, the recognition that a proportion of Hodgkin's disease tumours harbour the Epstein-Barr virus (EBV) and that its genome is monoclonal in these tumours suggests that the virus contributes to the development of Hodgkin's disease in some cases. This review summarises current knowledge of the pathogenesis of Hodgkin's disease with particular emphasis on the association with EBV.
Subject(s)
Herpesviridae Infections/complications , Herpesvirus 4, Human/genetics , Hodgkin Disease/etiology , Tumor Virus Infections/complications , Adolescent , Adult , Age Factors , Aged , Antibodies, Viral/immunology , Child , Child, Preschool , Female , Gene Expression , Genome, Viral , Hodgkin Disease/classification , Hodgkin Disease/genetics , Humans , In Situ Hybridization , Infant , Infant, Newborn , Male , Middle Aged , Polymerase Chain Reaction , Reed-Sternberg Cells/physiology , Sex Factors , Socioeconomic FactorsABSTRACT
A number of studies in developed countries have reported variation in the frequency of Epstein-Barr virus (EBV)-associated Hodgkin's disease (HD) with age. A 'three disease' model for HD that incorporates the EBV association, histological subtype of HD and age has recently been proposed. In this model, Hodgkin's disease of childhood and older adults is commonly EBV-associated and of mixed cellularity type, whereas young adult HD is generally not EBV-associated and is usually characterised by nodular sclerosis disease. A case series of HD diagnosed in the West Midlands between 1981 and 1997, inclusive, was used to investigate the applicability of the 'three disease' model. In situ hybridisation for the EBV early RNAs (EBERs) was used to determine the presence of EBV in the malignant Hodgkin/Reed-Sternberg cells. In contrast to the 'three disease' model, nodular sclerosis was the predominant subtype in each of the age groups within the case series. In addition, overall there was little variation in EBV-positive rates across the age ranges examined. However, when females were analysed separately, older women (45+ years) were significantly more likely to have EBV-positive disease than their younger counterparts (<45 years). In summary our results do not generally support the 'three disease' model.
Subject(s)
Epstein-Barr Virus Infections/epidemiology , Herpesvirus 4, Human , Hodgkin Disease/epidemiology , Adolescent , Adult , Age Distribution , Aged , Child , Child, Preschool , Female , Herpesvirus 4, Human/isolation & purification , Hodgkin Disease/classification , Hodgkin Disease/pathology , Hodgkin Disease/virology , Humans , Incidence , Infant , Male , Middle Aged , Registries , Retrospective Studies , United Kingdom/epidemiologyABSTRACT
The Epstein-Barr virus (EBV) has been linked to the development of a variety of human malignancies, including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, some T cell lymphomas, post-transplant lymphoproliferative disease, and more recently, certain cancers of the stomach and smooth muscle. This review summarizes these associations and in particular the role of the viral latent genes in the transformation process.
