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Infectious Mononucleosis, Childhood Social Environment, and Risk of Hodgkin Lymphoma

¹ Department of Epidemiology Research, Statens Serum Institut and ² Institute of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; ³ Institute of Medical Epidemiology and Biostatistics and ⁴ Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; ⁵ Departments of Oncology, Radiology, and Clinical Immunology and ⁶ Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; ⁷ Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark; and ⁸ Northern California Cancer Center, Fremont, and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California

Requests for reprints: Henrik Hjalgrim, Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark. Phone: 45-3268-3961; Fax: 45-3268-3165; E-mail: hhj{at}ssi.dk.

Infectious mononucleosis (IM) has been associated with an increased risk of Hodgkin lymphoma (HL), implicating a role for Epstein-Barr virus (EBV) in HL development. Although essential to the understanding of the association, it has remained uncertain if the relationship is restricted to the EBV-positive subset of HL. We collected information on mononucleosis history and childhood socioenvironmental characteristics in a population-based study of 586 patients with classic HL and 3,187 controls in Denmark and Sweden. Tumor EBV status was established for 499 cases by immunohistochemistry and in situ hybridization techniques. Odds ratios (OR) for the relationship between HL risk and mononucleosis and other risk factors were estimated by logistic regression for HL in younger (18–44 years) and older (45–74 years) adults, overall and by tumor EBV status. All analyses were adjusted for country-specific measures of maternal education and mononucleosis history. IM was associated with an increased risk of EBV-positive [OR, 3.23; 95% confidence interval (95% CI) 1.89–5.55] but not EBV-negative HL (OR, 1.35; 95% CI, 0.86–2.14). Risk of EBV-positive HL varied with time since IM and was particularly pronounced in younger adults (OR, 3.96; 95% CI, 2.19–7.18). IM-associated lymphomas occurred with a median of 2.9 years (1.8–4.9 years) after infection. The EBV specificity of the IM association was corroborated by a case-case comparison of IM history between younger adult EBV-positive and EBV-negative HL patients (OR_{IM EBV+ HL versus EBV– HL}, 2.68; 95% CI, 1.40–5.12). We found further evidence that IM is associated only with EBV-positive HL. This finding is compatible with the notion that EBV-positive and EBV-negative HL may have different etiologies. [Cancer Res 2007;67(5):2382–8]

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