Risk of Hodgkin's disease and other cancers after infectious mononucleosis.

BACKGROUND Infectious mononucleosis, which is caused by the Epstein-Barr virus, has been associated with an increased risk for Hodgkin's disease. Little is known, however, about how infectious mononucleosis affects long-term risk of Hodgkin's disease, how this risk varies with age at infectious mononucleosis diagnosis, or how the risk for Hodgkin's disease varies in different age groups. In addition, the general cancer profile among patients who have had infectious mononucleosis has been sparsely studied. METHODS Population-based cohorts of infectious mononucleosis patients in Denmark and Sweden were followed for cancer occurrence. The ratio of observed-to-expected numbers of cancers (standardized incidence ratio [SIR]) served as a measure of the relative risk for cancer. SIRs of Hodgkin's disease in different subsets of patients were compared with the use of Poisson regression analysis. All statistical tests including the trend tests were two-sided. RESULTS A total of 1381 cancers were observed during 689 619 person-years of follow-up among 38 562 infectious mononucleosis patients (SIR = 1. 03; 95% confidence interval [CI] = 0.98-1.09). Apart from Hodgkin's disease (SIR = 2.55; 95% CI = 1.87-3.40; n = 46), only skin cancers (SIR = 1.27; 95% CI = 1.13-1.43; n = 291) occurred in statistically significant excess. In contrast, the SIR for lung cancer was reduced (SIR = 0.71; 95% CI = 0.58-0.86; n = 102). The SIR for Hodgkin's disease remained elevated for up to two decades after the occurrence of infectious mononucleosis but decreased with time since diagnosis of infectious mononucleosis (P: for trend <.001). The SIR for Hodgkin's disease tended to increase with age at diagnosis of infectious mononucleosis (P: for trend =.05). Following infectious mononucleosis, the SIR for Hodgkin's disease at ages 15-34 years was 3.49 (95% CI = 2.46-4.81; n = 37), which was statistically significantly higher than the SIR for any other age group (P: for difference =.001). CONCLUSION The increased risk of Hodgkin's disease after the occurrence of infectious mononucleosis appears to be a specific phenomenon.

[1]  N. Harris,et al.  Evaluation of epstein‐barr virus antibody patterns and detection of viral markers in the biopsies of patients with Hodgkin's disease , 1994, International journal of cancer.

[2]  G. M. Taylor,et al.  Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents , 2000, British Journal of Cancer.

[3]  S. Glaser,et al.  Epidemiology of Hodgkin's disease. , 1996, Lancet.

[4]  N. Harris,et al.  Hodgkin's disease and Epstein-Barr virus. Altered antibody pattern before diagnosis. , 1989, The New England journal of medicine.

[5]  P. Hartge,et al.  Quantification of the impact of known risk factors on time trends in non-Hodgkin's lymphoma incidence. , 1992, Cancer research.

[6]  G. Kvåle,et al.  Hodgkin's disease in patients with previous infectious mononucleosis , 1979, International journal of cancer.

[7]  S. Hamilton-Dutoit,et al.  Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease , 1991, The Lancet.

[8]  H. A. Kahn,et al.  Statistical Methods in Epidemiology , 1989 .

[9]  R. Connelly,et al.  A cohort study of cancer following infectious mononucleosis. , 1974, Cancer research.

[10]  L. Caplan,et al.  Self-reported infectious mononucleosis and 6 cancers: a population-based, case-control study. , 1998, Scandinavian journal of infectious diseases.

[11]  C. la Vecchia,et al.  Socio‐economic indicators, infectious diseases and hodgkin's disease , 1991, International journal of cancer.

[12]  Gutensohn Nm.  Social class and age at diagnosis of Hodgkin's disease: new epidemiologic evidence for the "two-disease hypothesis". , 1982 .

[13]  R. Warnke,et al.  Epstein-Barr viral DNA in tissues of Hodgkin's disease. , 1987, The American journal of pathology.

[14]  B. Macmahon.  Epidemiology of Hodgkin's disease. , 1966, Cancer research.

[15]  G. de‐Thé,et al.  Infectious mononucleosis and Hodgkin's disease , 1978, International journal of cancer.

[16]  G. Beebe,et al.  Infectious mononucleosis and the empirical risk of cancer. , 1973, Journal of the National Cancer Institute.

[17]  G. Pinkus,et al.  Epstein-Barr virus in Hodgkin's disease: correlation of risk factors and disease characteristics with molecular evidence of viral infection. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[18]  N. Gutensohn,et al.  Childhood social environment and Hodgkin's disease. , 1981, The New England journal of medicine.

[19]  S. Glaser,et al.  Time trends in Hodgkin's disease incidence: The role of diagnostic accuracy , 1990, Cancer.

[20]  L. Stanberry,et al.  Preface to the fifth edition , 2014 .

[21]  P. Brousset,et al.  Epstein‐Barr virus‐associated Hodgkin's disease: Epidemiologic characteristics in international data , 1997, International journal of cancer.

[22]  M. Pike,et al.  Risk factors for nodular sclerosis and other types of Hodgkin's disease. , 1979, Cancer research.

[23]  T. M. Brown,et al.  Cancer incidence following infectious mononucleosis. , 1977, American journal of epidemiology.

[24]  S. Karjalainen,et al.  Patients treated in hospital for infectious mononucleosis and risk of cancer. , 1993, Scandinavian journal of infectious diseases.

[25]  B. Glimelius,et al.  Lymphoma incidence in a Swedish county during 1969-1987. , 1992, Acta oncologica.

[26]  S. Larsen,et al.  Hodgkin's Disease in Patients with Previous Infectious Mononucleosis: 30 Years' Experience , 1974, British medical journal.

[27]  N. E. Breslow.  Statistical Methods in Cancer Research , 1986 .

[28]  N. Koch-Henriksen,et al.  Increased risk of multiple sclerosis after late Epstein‐Barr virus infection*: A historical prospective study * , 1994 .

[29]  D. Wright,et al.  Epstein–Barr virus and Hodgkin’s disease: further evidence for the three disease hypothesis , 1998, Leukemia.

[30]  L. Avioli,et al.  Hodgkin's disease , 1969, Bone Marrow Transplantation.

[31]  G. Klein,et al.  Lack of correlation between EBV serology and presence of EBV in the Hodgkin and Reed‐Sternberg cells of patients with Hodgkin's disease , 1997, International journal of cancer.

[32]  N. Gutensohn.  Social class and age at diagnosis of Hodgkin's disease: new epidemiologic evidence for the "two-disease hypothesis". , 1982, Cancer treatment reports.

[33]  A. Mares,et al.  HIT AND RUN , 1999 .

[34]  A. Jarrett,et al.  Epidemiology of EBV and Hodgkin's lymphoma. , 1996, Annals of oncology : official journal of the European Society for Medical Oncology.

[35]  N. Gutensohn,et al.  A population‐based case‐control study of EBV and other viral antibodies among persons with Hodgkin's disease and their siblings , 1984, International journal of cancer.

[36]  Robert W. Miller,et al.  Infectious Mononucleosis and the Empirical Risk off Cancer , 1973 .

[37]  R. Ambinder.  Gammaherpesviruses and "Hit-and-Run" oncogenesis. , 2000, The American journal of pathology.

[38]  B Mattsson,et al.  Completeness of the Swedish Cancer Register. Non-notified cancer cases recorded on death certificates in 1978. , 1984, Acta radiologica. Oncology.

[39]  C. Bird,et al.  Hodgkin's disease: case control epidemiological study in Yorkshire. , 1987, British Journal of Cancer.

[40]  H. Storm,et al.  The Danish Cancer Registry--history, content, quality and use. , 1997, Danish medical bulletin.

[41]  A. Evans,et al.  Epstein-Barr Virus , 1982 .