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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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CLINICAL TRIALS AND OBSERVATIONS
Interleukin-2, interleukin-12, and interferon- levels and risk of young adult Hodgkin lymphoma
Wendy Cozen1,2,
Parkash S. Gill3,
Muhammad T. Salam1,
Alexandra Nieters4,
Rizwan Masood5,
Myles G. Cockburn1,
W. James Gauderman1,
Otoniel Martínez-Maza6,
Bharat N. Nathwani2,
Malcolm C. Pike1,
David J. Van Den Berg7,
Ann S. Hamilton1,
Dennis M. Deapen1, and
Thomas M. Mack1,2
1 Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles;
2 Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles;
3 Department of Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles;
4 German Cancer Research Center, Heidelberg, Germany;
5 Department of Otolaryngology, Keck School of Medicine, University of Southern California, Los Angeles;
6 Departments of Obstetrics & Gynecology and Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA); and
7 Department of Urology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles
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 cotwins), and 90 matched controls. Mean difference and mean percentage difference in cytokine levels between case-twins and controls, and unaffected cotwins and controls were determined using analysis of covariance. YAHL case-twins and their unaffected cotwins had IL-12 levels that were 60.6% (P = .002) and 49% (P = .04) lower than those of their matched controls, respectively. IL-2 levels were significantly higher in case-twins (P = .049), but not unaffected cotwins (P = .57), compared with 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 = .03) increase in YAHL risk. Thus, both case-twins and their unaffected cotwins had a decreased ability to produce IL-12, which may contribute to YAHL susceptibility.
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