Cytokine signaling pathway polymorphisms and AIDS-related non-Hodgkin lymphoma risk in the multicenter AIDS cohort study
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.
- SourceAvailable from: Jing He
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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. "
ABSTRACT: A number of studies have investigated the associations between IL-10 polymorphisms and non-Hodgkin lymphoma (NHL) susceptibility; however, the conclusions were still contradictory. To acquire a more precise estimation of the association, we performed the current meta-analysis. We systematically searched publications from EMBASE and MEDLINE, and calculated pooled odds ratios (ORs) and 95 % confidence intervals (CIs) using either fixed-effects or random-effects model. Genotype-based IL-10 mRNA expression analysis was performed using online public database of 270 individuals with three different ethnicities. A total of 10,703 cases and 11,823 controls from 10 studies were included for the -3575T>A polymorphism, 10,226 cases and 12,215 controls from 17 studies for the -1082A>G polymorphism. Pooled results indicated that IL-10 -3575T>A was associated with increased risk of diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL), especially for Caucasians and hospital-based population. There was no association between IL-10 -1082A>G and NHL risk. However, subgroup analysis showed that IL-10 -1082GG might confer increased susceptibility to FL. In summary, this meta-analysis indicated that -3575T>A polymorphism was associated with altered NHL susceptibility for Caucasians and hospital-based population, especially for DLBCL and FL subtypes. The -1082A>G polymorphism may contribute to increased FL risk. Further large-scale population studies among different ethnicities are needed to validate these results.Molecular Genetics and Genomics 04/2015; DOI:10.1007/s00438-015-1058-y · 2.83 Impact Factor
Article: Cancer biomarkers in HIV patients[Show abstract] [Hide abstract]
ABSTRACT: In this review, we update investigations related to cancer biomarkers in HIV-infected populations. CD4 lymphocyte count is associated with primary central nervous system lymphoma (PCNSL), systemic non-Hodgkin's lymphoma (NHL) (except perhaps for Burkitt lymphoma), Kaposi's sarcoma, cervical cancer, and anal cancer. HIV load is associated with Burkitt lymphoma and systemic NHL (but not PCNSL), with Kaposi's sarcoma and with anal cancer. CD40 ligand incorporated into the HIV envelope and expression of activation-induced cytidine deaminase may help explain the relationship between HIV load and Burkitt lymphoma. Genetic polymorphisms have been identified that are linked to lymphoma in HIV patients. B-cell activation as manifest in immunoglobulin light chain production may be an important marker for NHL risk. Cytokines and related molecules (IL10, sCD30) may identify patients at high risk for NHL. Epstein-Barr virus (EBV) in cerebrospinal fluid (CSF) is useful as a marker for PCNSL, although with the falling incidence of PCNSL, the specificity of the test has been called into question. EBV and Kaposi's sarcoma-associated herpesvirus (KSHV) have not yet emerged as especially promising markers of risk for either lymphoma or Kaposi's sarcoma. CD4 lymphocyte count, HIV load, germline genetic polymorphisms, cytokine and related molecules, and immunoglobulin light chains all show increasing promise as biomarkers of malignancy in HIV patients.Current opinion in HIV and AIDS 11/2010; 5(6):531-7. DOI:10.1097/COH.0b013e32833f327e · 4.39 Impact Factor
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ABSTRACT: HIV infection is associated with a much higher risk for the development of non-Hodgkin lymphoma (AIDS-NHL). The principal causes of lymphomagenesis in HIV-infected individuals are thought to be the loss of immune function seen in HIV infection, which results in the loss of immunoregulation of Epstein-Barr virus-infected B cells, as well as HIV infection-associated immune dysregulation, including chronic B-cell activation. In this review, we discuss recent reports that further support the importance of these factors, and we highlight emerging evidence of different mechanisms that potentially drive lymphomagenesis in HIV-infected individuals.Immunologic Research 12/2010; 48(1-3):72-83. DOI:10.1007/s12026-010-8168-8 · 3.53 Impact Factor