Article

Cytokine signaling pathway polymorphisms and AIDS-related non-Hodgkin lymphoma risk in the multicenter AIDS cohort study

National Cancer Institute, Rockville, Maryland, USA.
AIDS (London, England) (Impact Factor: 6.56). 03/2010; 24(7):1025-33. DOI: 10.1097/QAD.0b013e328332d5b1
Source: PubMed

ABSTRACT 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.
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).
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.
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.

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    • "Dysfunctions in the immune system are thought to be the underlying basis of lymphomagenesis (Wu and Cheng 2014). Numerous studies have reported the possible involvement of IL-10 polymorphisms in the pathogenesis of lymphoid malignancies (Andrie et al. 2009; Berglund et al. 2005; Cunningham et al. 2003; Fernberg et al. 2010; Guzowski et al. 2005; Hosgood et al. 2013; Kube et al. 2007; Lan et al. 2006; Lech-Maranda et al. 2004, 2007, 2013; Nieters et al. 2006; Persico et al. 2006; Purdue et al. 2007b; Rothman et al. 2006; Wang et al. 2006; Wong et al. 2010; Yri et al. 2013). IL-10 −3575T>A and −1082A>G were the most well-characterized polymorphisms in the IL-10 gene. "
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