Abstract 2537: Infectious, autoimmune, and allergic diseases and risk of Hodgkin lymphoma in children and adolescents: A Children's Oncology Group (COG) study.
Authors: Linabery Amy M. , Erhardt Erik B. , Fonstad Rachel K. , Grufferman Seymour , Ambinder Richard F. , Bunin Greta R. , Ross Julie A. , Spector Logan G. 
Published: August 2014

Abstract
Relatively little research has been devoted to understanding the causes of Hodgkin lymphoma (HL) in children. HL diagnosed at &lt;15 years has incidence patterns and clinical characteristics distinct from HL in older adolescents and adults. Because of these differences, different underlying causes have also been postulated. Nevertheless, similar to adult HL, an infectious origin for pediatric HL has long been suspected and Epstein-Barr virus (EBV) has been implicated in a subset of cases. Results of genome-wide association studies in adult HL, consistent associations between autoimmune diseases and HL in adults, and increased HL incidence in children with congenital and acquired immunodeficiencies together suggest a role for immune dysregulation in lymphomagenesis. Here we examined associations between personal and family histories of infectious, autoimmune, and allergic diseases and HL in children and adolescents using data from the largest case-control study conducted to date. Healthy control children identified by random digit dialing were matched on sex, race/ethnicity, and date of birth to cases diagnosed in 1989-2003 at 0-14 years at North American COG institutions. Parents of 517 cases and 784 controls completed standardized 1-hour telephone interviews, including items regarding medical histories. Tumor EBV status was determined by detection of EBV-encoded RNAs via digoxigenin-based in situ hybridization. Using multivariate conditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for risk of HL overall, and by tumor EBV status (EBV+, EBV-) and HL subtypes (nodular sclerosis, mixed cellularity, lymphocyte predominant) after adjusting for income, education, and birth order. Cases (OR=1.79, 95% CI: 1.04-3.08) were more likely to have had an infection &gt;1 year prior to HL diagnosis, and EBV+ cases were more likely to report prior sore throats (including strep throat, scarlet fever, tonsillitis; OR=2.19, 95% CI: 1.06-4.53) and infectious mononucleosis (OR=9.10, 95% CI: 0.81-102.3). Case siblings were also more likely to have had an infection prior to HL diagnosis (OR=2.04, 95% CI: 1.01-4.14). In index children, autoimmune (OR=0.46, 95% CI: 0.16-1.38) and allergic (OR=1.22, 95% CI: 0.93-1.59) diseases identified &gt;1 year before HL diagnosis were not associated with HL overall or by EBV status or subtype. There were no notable associations for autoimmune or allergic diseases in parents or siblings. These results may indicate a true increased risk for infections and lack of association with history of conditions imparting immune dysregulation, or they may be attributable to inaccurate recall. Future studies should employ biomarkers to understand differences in immune function preceding pediatric HL.
Supported by NIH Grants R01 CA047473 and K05 CA157439, and Children's Cancer Research Fund, Minneapolis, MN.
Citation Format: Amy M. Linabery, Erik B. Erhardt, Rachel K. Fonstad, Seymour Grufferman, Richard F. Ambinder, Greta R. Bunin, Julie A. Ross, Logan G. Spector. Infectious, autoimmune, and allergic diseases and risk of Hodgkin lymphoma in children and adolescents: A Children's Oncology Group (COG) study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2537. doi:10.1158/1538-7445.AM2013-2537
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.