Background: Cytokine stimulation of B-cell proliferation may be an important causative mechanism for acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). The Epstein–Barr virus (EBV) may be a co-factor, particularly for primary central nervous system (CNS) tumors, which are uniformly EBV-positive in the setting of AIDS. Thus, we examined associations of genetic variation in IL10 and related cytokine-signaling molecules (IL10RA, CXCL12, IL13, IL4, IL4R, CCL5 and BCL6) with AIDS-related NHL risk and evaluated differences between primary CNS and systemic tumors.
Patients and materials: We compared 160 Multicenter AIDS Cohort Study (MACS) participants with incident lymphomas, of which 90 followed another AIDS diagnosis, to HIV-1-seropositive controls matched on duration of lymphoma-free survival post-HIV-1 infection (N = 160) or post-AIDS diagnosis (N = 90). We fit conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
Results: Carriage of at least one copy of the T allele for the IL10 rs1800871 (as compared to no copies) was associated with decreased AIDS-NHL risk specific to lymphomas arising from the CNS (CC vs. CT/TT: OR = 0.3; 95% CI 0.1, 0.7) but not systemically (CC vs. CT/TT: OR = 1.0; 95% CI 0.5, 1.9) (Pheterogeneity = 0.03). Carriage of two copies of the ‘low IL10’ haplotype rs1800896_A/rs1800871_T/rs1800872_A was associated with decreased lymphoma risk that varied by number of copies (Ptrend = 0.02). None of the ORs for the other studied polymorphisms was significantly different from 1.0.
Conclusion: Excessive IL10 response to HIV-1 infection may be associated with increased risk of NHL, particularly in the CNS. IL10 dysregulation may be an important causative pathway for EBV-related lymphomagenesis.
aNational Cancer Institute, Rockville, Maryland, USA
bDavid Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
cUniversity of Alabama at Birmingham, Birmingham, Alabama, USA
dUniversity of Pittsburgh, Pittsburgh, Pennsylvania, USA
eJohns Hopkins University, Baltimore, Maryland, USA.
Received 23 April, 2009
Revised 2 September, 2009
Accepted 9 September, 2009
Correspondence to Hui-Lee Wong, MSc, PhD, Division of Epidemiology, Office of Surveillance and Biometrics, Center for Devices and Radiological Health, FDA WO66-4561, 10903 New Hampshire Av. Silver Spring, MD 20993-0002, USA. Tel: +1 301 796 6234; fax: +1 301 847 8140; e-mail: email@example.com