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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3310. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ambinder, R. F. Search for Related Content PubMed Articles by Ambinder, R. F. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS Comment on Cozen et al, page 3377 Hodgkin twins: double good, double trouble Richard F. Ambinder JOHNS HOPKINS SCHOOL OF MEDICINE In this issue of Blood, Cozen and colleagues report on cytokine levels and the presence of a genetic polymorphism in the twins of patients with young-adult Hodgkin lymphoma. The analysis focuses on interleukin-12 in monozygotic twins, dizygotic twins, and control donors. The results suggest an interesting hypothesis that builds on the "polio" and "hygiene" hypotheses that have previously been offered to explain the epidemiology of young-adult Hodgkin lymphoma. The higher incidence of young-adult Hodgkin lymphoma in more affluent populations with smaller family sizes has long attracted the interest of epidemiologists. In the prevaccine era, poliomyelitis, the devastating consequence of poliovirus infection, was much more common in those who were infected in adolescence or early adulthood rather than in those infected in early childhood, during which the major manifestation of poliovirus infection was a diarrheal illness. It was proposed that the age-incidence curve of Hodgkin lymphoma in Western countries, with a young-adult peak, might also reflect the consequence of a common infection that was delayed until adolescence or early adulthood.1,2 When Epstein-Barr virus DNA was found to be present in the tumor cells of a subset of Hodgkin lymphoma patients, it appeared that this ubiquitous viral infection might explain the epidemiology of young-adult Hodgkin lymphoma. However, although there is a clear link between symptomatic infectious mononucleosis and Hodgkin lymphoma, the link is only between infectious mononucleosis and EBV+ Hodgkin lymphoma. EBV– Hodgkin lymphoma appears not to be increased in people with a history of infectious mononucleosis.3 And since most young-adult Hodgkin lymphoma is EBV–, further explanations were needed.4 Enter the "hygiene" hypothesis. Originally invoked to explain an increased susceptibility to allergic diseases, this hypothesis holds that lack of early childhood exposure to a variety of infectious agents perturbs immune development in a sometimes deleterious way. Could immune dysfunction related to exposure to childhood pathogens be important in the development of Hodgkin disease? Cozen and colleagues had previously used a remarkable twin registry to demonstrate a genetic susceptibility to Hodgkin lymphoma.5 In the present report, Cozen et al return to their twin registries, now reporting that low levels of IL-12 may be a risk factor for Hodgkin lymphoma and that IL-12 levels may be determined by exposure to a variety of childhood infections and host genetics. So far, double good. There is, however, double trouble. Although the authors studied cytokine production and genetic polymorphism in the same subjects, they are unable to link the 2 sets of data. The consent form used to collect blood specimens did not mention genetic analyses, and in order to study genetics, it was necessary to break linkages. Although cytokine production analysis and genetic analysis would seem to support the general hypothesis offered, there remains the possibility that, if the data were linked, the IL-12 levels might not be associated with the genetic polymorphism, or that the association might be the inverse of what the investigators anticipated. Thus the investigators have offered an interesting hypothesis to explain aspects of the epidemiology of young-adult Hodgkin lymphoma. However, the case is not yet closed, and Hodgkin investigators will have to redouble their efforts in the future. Footnotes Conflict-of-interest disclosure: The author declares no competing financial interests. REFERENCES Grufferman S and Delzell E. Epidemiology of Hodgkin's disease. Epidemiol Rev 1984; 6:76–106.[Free Full Text] Mueller N, Evans A, Harris NL, et al. Hodgkin's disease and Epstein-Barr virus. Altered antibody pattern before diagnosis. N Engl J Med 1989; 320:689–695.[Abstract] Hjalgrim H, Smedby KE, Rostgaard K, et al. Infectious mononucleosis, childhood social environment, and risk of Hodgkin lymphoma. Cancer Res 2007; 67:2382–2388.[Abstract/Free Full Text] Glaser SL, Lin RJ, Stewart SL, et al. Epstein-Barr virus-associated Hodgkin's disease: epidemiologic characteristics in international data. Int J Cancer 1997; 70:375–382.[CrossRef][Medline] [Order article via Infotrieve] Mack TM, Cozen W, Shibata DK, et al. Concordance for Hodgkin's disease in identical twins suggesting genetic susceptibility to the young-adult form of the disease. N Engl J Med 1995; 332:413–418.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Interleukin-2, interleukin-12, and interferon- levels and risk of young adult Hodgkin lymphoma Wendy Cozen, Parkash S. Gill, Muhammad T. Salam, Alexandra Nieters, Rizwan Masood, Myles G. Cockburn, W. James Gauderman, Otoniel Martínez-Maza, Bharat N. Nathwani, Malcolm C. Pike, David J. Van Den Berg, Ann S. Hamilton, Dennis M. Deapen, and Thomas M. Mack Blood 2008 111: 3377-3382. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ambinder, R. F. Search for Related Content PubMed Articles by Ambinder, R. F. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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