A specialist leukaemia/lymphoma registry in the UK. Part 2: clustering of Hodgkin's disease

Abstract

Summary Part 1 describes the epidemiology of Hodgkin's disease occurring in those parts of the United Kingdom which are included in the Leukaemia Research Fund data collection survey. A total of 1,023 cases diagnosed between 1984 and 1986 were available for analysis. At county and district levels there was little heterogeneity in the distribution of cases. However, at the electoral ward level there were real differences for the younger age group . In this paper methods of investigation which are not dependent on census boundaries are applied and the presence of localised spatial clustering is confirmed. There is some evidence that the pattern of clustering relates to the nodular sclerosing subtype. These results are related to hypotheses of an infectious aetiology.The distribution of Hodgkin's disease has raised questions of long-standing interest to epidemiologists. The unusual agedistribution was first noted by MacMahon (1966), who suggested that it might result from a combination of two distinct diseases. From the histological appearance, clinical course and anatomical distribution of the lesions as well as the age distribution he postulated an infectious aetiology in those aged less than 35 and an aetiology similar to other lymphomas in cases over 50. Subsequent research is in broad agreement with the two disease hypothesis (Roush, 1987;Gutensohn, 1982). Evidence for a viral aetiology comes from anecdotal reports of micro-clusters and of case linkage (Vianna et al., 1971;Grufferman et al., 1977), from school cohort studies (Vianna & Polan, 1973), formal analyses of space-time interaction (Kryscio et al., 1973;Greenberg et al., 1983), case-control studies of social linkage (Zack et al., 1977;Scherr et al., 1984), and follow-up of cases of infectious mononucleosis (Rosendahl, 1974; Muellar, 1987). Although the evidence is inconclusive and somewhat conflicting there is a consensus that an infectious aetiology is more likely for younger cases.The Leukaemia Research Fund data collection survey has been described (McKinney et al., 1989) and the basic descriptive epidemiology of Hodgkin's disease reported. This showed some evidence of localised aggregations of cases, or 'clustering', for the younger age group. The present study concentrates on spatial clustering using more sophisticated methods of analysis which do not depend on arbitrary administrative boundaries. MethodsIncidence data have been taken from the Leukaemia Research Fund data collection survey (DCS) described earlier (McKinney et al., 1989 al., 1989;Besag, 1989) and by control locations in the second (Cuzick & Edwards, 1989). Both provide global tests of the extent of localised spatial clustering. The NNA method involves consideration of each case in turn. We first identify the two nearest cases and then estimate the population from which these cases derived. If the expected number in this population is significantly small (P<0.05) then the case is the centre of a small local aggregation and is said to be 'clustered'. In a random distribution approxi...

Viral involvement in Hodgkin's disease: detection of clonal type A Epstein-Barr virus genomes in tumour samples

“…These studies support the hypothesis that HD in younger persons may arise as an unusual and late host response to a common infectious agent. Alexander et al (1989) found evidence of local spatial clustering of young cases of HD, particularly of the nodular sclerosing subtype supporting the hypothesis that case to case transmission of an infectious agent is involved.…”

“…NSHD is the predominant subtype amongst young adults and Alexander et al (1989) have reported evidence of clustering of both NSHD and of cases aged < 35 years.…”

Lymphohaematopoietic malignancy around all industrial complexes that include major oil refineries in Great Britain.

“…19 The decline in risk with distance from oil refineries for Hodgkin's disease must be viewed in the context of multiple testing and the general tendency of Hodgkin's disease to cluster. 20 That benzene might be a contributory factor in Hodgkin's disease has been hypothesised by Aksoy et al, 21 and there have been reported associations of Hodgkin's disease with occupation in the chemical industry, 22 with other occupations entailing handling of chemicals, [23][24][25] and with exposure to diesel exhaust. 26 However, none of these studies provides direct evidence relating to the petrochemical industry.…”

A specialist leukaemia/lymphoma registry in the UK. Part 1: incidence and geographical distribution of Hodgkin's disease

“…However, no previous work has documented the geographical distribution of HD at varying levels and it is of interest that the disease appears in a homogeneous pattern on a large scale but small areas reveal significant heterogeneity. Examination of these data for evidence of clustering is subsequently described (Alexander et al, 1989b variable E1; however, the division of opinion between the use of incidence ratios and P values has been ubiquitous at least since the Black report (Black, 1984) which used both. The problem with sparse data is that incidence ratios are unstable and lack precision, particularly for the smallest Eis while P values depend on the value of Ei in a complex way (because of discreteness of the Poisson distribution) but tend to favour larger areas.…”