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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3377-3382.
Prepublished online as a Blood First Edition Paper on December 12, 2007; DOI 10.1182/blood-2007-08-106872.
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Submitted August 13, 2007
Accepted November 3, 2007
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 Martinez-Maza, Bharat N. Nathwani, Malcolm C. Pike, David. J. Van Den Berg, Ann S. Hamilton, Dennis M. Deapen, and Thomas M. Mack
Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United States
Department of Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United States
Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany
Department of Otolaryngology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
Departments of Obstetrics & Gynecology and Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
Department of Urology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United States
* Corresponding author; email: wcozen{at}usc.edu.
Young adult Hodgkin lymphoma (YAHL) is associated clinically with altered immunity, including a systemic defect in cell-mediated responses. There is strong evidence of a genetic contribution to risk so we hypothesized that heritable alterations in cytokine production associated with Th1 function may contribute to susceptibility. We identified twin pairs in whom at least one member had YAHL and measured interleukin-2 (IL-2), interleukin-12 (IL-12) and interferon- (IFN-) levels in PHA-stimulated peripheral blood mononuclear cell supernatant in 90 case-twins, 84 of their disease-free twins (unaffected co-twins), and 90 matched controls. Mean difference and mean percent difference in cytokine levels between case-twins and controls, and unaffected co-twins and controls were determined using analysis of co-variance. YAHL case-twins and their unaffected co-twins had IL-12 levels that were 60.6% (p=0.002) and 49% (p=0.04) lower than those of their matched controls, respectively. IL-2 levels were significantly higher in case-twins (p=0.049), but not unaffected co-twins (p=0.57), compared to controls. Differences in IFN- levels were not statistically significant in either comparison. An IL-12 polymorphism known to regulate expression was associated with a 2.8-fold (p=0.03) increase in YAHL risk. Thus both case-twins and their unaffected co-twins had a decreased ability to produce IL-12, which may contribute to YAHL susceptibility.
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