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

Abstract

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 EBVpositive 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,). 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 casecase comparison of IM history between younger adult EBVpositive and EBV-negative HL patients (OR IM EBV+ HL versus EBVÀ 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]

Exposure to UV radiation and risk of Hodgkin lymphoma: a pooled analysis

“…Numerous epidemiologic studies have identified a variety of putative risk factors as well as substantial etiologic heterogeneity based on age group at diagnosis, tumor histologic subtype, and the presence or absence of Epstein-Barr virus (EBV) in the malignant Hodgkin/Reed-Sternberg cells. [6][7][8][9][10] However, the causes of HL remain poorly understood, in part because its low incidence limits the study sample sizes needed for adequate statistical power, particularly for the stratified analyses necessary to accommodate HL heterogeneity. Further, while the presence of EBV in HL tumors in selected patient subsets has been an important etiologic observation, the etiologic role of this virus in EBV-negative HL, which comprises the majority of cases, remains unclear.…”

“…Further, while the presence of EBV in HL tumors in selected patient subsets has been an important etiologic observation, the etiologic role of this virus in EBV-negative HL, which comprises the majority of cases, remains unclear. 7,9 Ultraviolet radiation (UVR) exposure has been associated with HL risk, albeit inconsistently and based on only a few studies. [11][12][13][14][15][16] A large population-based case-control study in Sweden and Denmark detected an inverse association between risk of HL and sunbathing or There is an Inside Blood commentary on this article in this issue.…”

Hodgkin's lymphoma and infection: findings from a UK case–control study

“…A proportion is thought to be related to infection with Epstein Barr virus (EBV), which is integrated clonally into tumour cells in as many as 40% of cases (IARC, 1997). Elevated titres of antibodies against EBV have been associated with subsequent risk of Hodgkin's lymphoma, while infectious mononucleosis, known to be caused by EBV, is an established risk factor (Mueller et al, 1989;Hjalgrim et al, 2000Hjalgrim et al, , 2007. Elevated titres of antibodies against another human herpesvirus (type 6) have been found in some, but not in other studies (Clark et al, 1990;Jarrett et al, 1998;Berrington de González et al, 2006).…”

Vaccines and Antiviral Drugs for Diseases Associated with the Epstein-Barr Virus

“…8 Approximately 25%-50% of classical HL cases are associated with the presence of EBV in Reed-Sternberg (RS) mononuclear, and multinuclear cells, 9 which are major components of the tumor. 10 RS cells produce cytokines and chemokines, including TGF-B, IL-10, and TARC. These cytokines and chemokines possibly enable RS cells to modulate the immune response and escape CTL detection.…”