A population-based case-control study of EBV and other viral antibodies among persons with Hodgkin's disease and their siblings.

The Epstein-Barr virus (EBV) has been consistently found to be associated with Hodgkin's disease (HD) in two ways: cases generally have elevated titer distributions of antibodies against the viral capsid antigen, and the occurrence of HD among persons with a history of EBV infectious mononucleosis is two or three times higher than expected. We evaluated this association by measuring the prevalence and level of antibodies against EBV and related viruses among 304 cases of HD interviewed in a population-based study in comparison to 285 of their siblings. The most significant finding was that antibody titers to the viral capsid antigen of EBV were elevated (greater than or equal to 1:320) in 39% of the cases and in only 14% of the sibling-controls; the relative risk adjusted for age and sex was 4.1. The geometric mean titer was three-fold higher among cases (175.6 vs. 58.1) Subjects who reported a history of IM had a higher distribution of titers than those who did not. Cases also had elevated titers against the early antigen of EBV - the D Component being most prominent. A significantly higher proportion of cases has elevated titers against CMV, relative risk = 3.4, but the prevalence of CMV antibody was relatively low and not consistently higher among cases. The findings support the hypothesis that EBV may play a role in the pathogenesis of HD among persons with elevated titers. The findings neither confirm nor deny a possible role of CMV.

School contact among persons with Hodgkin's disease.

The authors evaluated the hypothesis that Hodgkin's disease is transmitted among high school students (in a contagious manner) by determining whether members of a population-based series of young adult cases attended school together more frequently than expected. Cases of Hodgkin's disease were diagnosed from July 1, 1973 through December 31, 1977. Of the 245 cases and 483 matched population controls interviewed, 196 cases and 371 controls attended schools in Massachusetts. School histories of subjects obtained by personal interviews were analyzed to determine the frequency with which subjects had been in the same class or had attended the same school at the same time. In high school, cases were schoolmates more often than expected (relative risk (RR) = 1.2), as well as classmates (RR = 1.9). However, in junior high school, cases were schoolmates less often than expected (RR = 0.8), and none were classmates with four expected. In elementary school, cases were somewhat more likely to be schoolmates (RR = 1.4) with no excess of classmates. The 95% confidence interval for all relative risks includes 1.0.

Association of the human type C retrovirus with a subset of adult T-cell cancers.

To determine whether the human T-cell lymphoma-leukemia virus (HTLV) is associated with particular cancers, patient sera were surveyed for HTLV-specific antibodies. An association was seen with aggressive cancers of mature T-cells, specifically Japanese adult T-cell leukemia (ATL) and T-cell lymphosarcoma cell leukemia (TLCL), a similar cancer of Caribbean blacks. Ninety to 100% of these patients possessed HTLV-specific antibody. Forty-seven and 20% of relatives of ATL and TLCL patients, respectively, and 12 and 4% of healthy donors from ATL and TLCL endemic areas were also antibody positive. Visceral organ involvement, hypercalcemia, and skin manifestation, features of ATL and TLCL, were often seen in other antibody-positive patients. Childhood cancers, most cutaneous T-cell and all non-T-cell leukemias and lymphomas, myeloid leukemias, Hodgkin's disease, and solid tumors were not associated with HTLV. Healthy United States donors and European patients with non-malignant diseases were antibody negative. HTLV is thus associated with a subtype of adult T-cell leukemia-lymphoma, clustered in viral endemic areas, with apparent racial and geographic predilection.

Social class risk factors among children with Hodgkin's disease.

We compared the social class characteristics of 66 families with children diagnosed with Hodgkin's disease (HD) from 1959 through 1977 in a defined population with that of 182 "control families" identified by a random process from the population base. The 14 youngest cases (less than 10 years at diagnosis) were from somewhat lower social-class backgrounds than their 37 controls as evidenced by the distribution of median income, single-unit housing, and poverty level of their census tract of residence, as well as by the occupational class of head-of-household. In contrast, the social class characteristics of the 52 older children with HD (10-14 years) were quite similar to that of their 145 controls. This apparent shift from lower to average social class between younger and older children with HD Hodgkin's disease may reflect a shift in their age of exposure to common infections. If true, these findings are consistent with the hypothesis that HD may develop as a rare consequence of a common infection. However, these findings are based on small numbers of cases and on indirect measures of social class.

Social class and age at diagnosis of Hodgkin's disease: new epidemiologic evidence for the "two-disease hypothesis".

The bimodality in the age-incidence pattern of Hodgkin's disease (HD) suggests that the disease may result from two causal pathways with differing age peaks. Among young adults, HD may develop as a rare consequence of a common infection (probably viral), with risk increasing with age at time of infection. However, among older persons, HD may result from other causes, probably similar to those of the other lymphomas. We evaluated this hypothesis in a population-based, case-control study in eastern Massachusetts involving 326 newly diagnosed cases (patients greater than or equal to 15 years of age) and 650 population controls. These subjects were compared for factors in childhood environment that influence age of exposure to common viruses, including sibship size, parental education, and type of housing. Among young adults (15-39 years of age), risk of HD was associated with small family size, single-family housing, and relatively high maternal education, consistent with the delayed infectious exposure hypothesis. Among middle-aged persons (40-54 years of age), a similar pattern of social class risk factors was present. However, among older persons (greater than or equal to 55 years of age), risk was not associated with social class; if anything, patients were of somewhat lower social class background than controls. These findings are consistent with the "two-disease hypothesis," in that social class risk factors differed between younger and older persons. These findings, coupled with other epidemiologic observations, suggest that the pathogenesis of HD among older persons is independent of that among younger persons.

Epidemiologic association between virus-negative feline leukemia and the horizontally transmitted feline leukemia virus.

About two-thirds of the natural cases of feline leukemia-lymphoma are assumed to be caused by the feline leukemia virus (FeLV) because they occur in cats, which harbor this agent, and FeLV will induce the disease under laboratory conditions. Epidemiological evidence is presented which associates cases of naturally occurring 'virus negative' feline leukemia with exposure to FeLV.

Childhood social environment and Hodgkin's disease.

The epidemiologic similarities between Hodgkin's disease in the young and paralytic poliomyelitis suggest that Hodgkin's disease may be a rare consequence of a common infection, with the probability of oncogenesis increasing with age at the time of infection. In a study of 225 cases and 447 controls 15 to 39 years of age, we investigated the association of Hodgkin's disease with factors in childhood that influence age of exposure to infectious agents. Risk among persons with five or more siblings was nearly half that among those with one or none; risk was also reduced among persons of late birth order. Subjects who had lived in multiple-family homes had half the risk of those in single-family housing. Cases had fewer playmates and better-educated mothers than did controls, and cases had twice the rate of infectious mononucleosis. Risk is therefore associated with a set of factors that tend to decrease or delay early exposure to infections, and this association might be explained by a viral origin of the disease, with age at infection as a major modifier of risk.

Epidemiology of hodgkin's disease in the young.

Many features of Hodgkin's disease (HD) among adolescents and young adults suggest that it has an infectious etiology. However, the proposal that HD is a contagious disease which can be transmitted by patients or their close contacts has not been substantiated. An alternative infectious disease model is suggested by analogy with paralytic poliomyelitis (PP). For both diseases, the peak age of incidence is delayed as living conditions improve. For both, increased risk is associated with higher social class and small family size. Like PP, HD may be a rare manifestation of a common infection with the probability of disease development increasing as age at infection is delayed. This analogy is supported by the report that the risk of HD is higher for persons who had a low frequency of childhood infectious diseases. If this model is valid, HD patients represent no hazard to their contacts. However, the incidence of HD among young adults may increase in the coming decade because of the current high standard of living and small family size.

Epstein-Barr virus-malaria interaction models for Burkitt's lymphoma: implications for preventive trials.

Infections with both Epstein-Barr virus (EBV) and malaria have been implicated as causal factors in the pathogenesis of Burkitt's lymphoma (BL). Proposed trials of preventive measures for both infections are receiving serious consideration as possible means of establishing a causal relationship with BL. In this paper we examine certain models for the interaction of EBV and malaria in the induction of BL, and also review the aims of the longitudinal, population-based study being conducted in the West Nile District of Uganda. Given existing knowledge, the outcome of preventive trials, even for the most simple interaction models, is unpredictable and, under certain circumstances, trials of an EBV vaccine could actually increase the incidence of BL. It is suggested that trials of an EBV vaccine at this time would be premature and should be delayed at least until the results from the West Nile prospective study are clear.

Hodgkin's Disease, tonsillectomy and family size.

The association of tonsillectomy and Hodgkin's disease was investigated by comparison of 136 young adult patients with their 315 siblings and 78 spouses. On the basis of a case-spouse comparison, the risk ratio of Hodgkin's disease among tonsillectomized persons was 3.1 (1.5 to 7.7, 95 per cent confidence limits); on the basis of a case-sibling comparison it was 1.4 (0.8-2.6). The case-sibling analysis was repeated according to sibship size, and increased risk of disease was associated with tonsillectomy only within the 37 sibships of size two. A similar variation of risk ratio with sibship size was found in data from a prior study. The range of the association implies that the relation beteeen tonsillectomy and Hodgkin's disease either is noncausal or is complex and modified by family size. Risk of Hodgkin's disease was found to increase as a sibship size decreased, suggesting that a cause of Hodgkin's disease is correlated with childhood social class.