Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD40 and its ligand, CD154, are major costimulatory molecules whose interactions are important in humoral and cellular immunity. We hypothesized that single nucleotide polymorphisms (SNPs) in TNFRSF5 and TNFSF5 encoding the CD40 and CD154 proteins, respectively, influence lymphoma risk, particularly a functional TNFRSF5 SNP (-1C>T, rs1883832) associated with reduced B-cell CD40 expression. TNFRSF5 and TNFSF5 SNPs were examined in a population-based case-control study of non-Hodgkin lymphoma (376 cases/801 controls with DNA), and compelling findings were followed up in 2 independent populations. Pooled analyses of all 3 case-control studies (total N = 1776 non-Hodgkin lymphoma cases, N = 2482 controls) revealed an increased risk of follicular lymphoma (FL) associated with the TNFRSF5 -1TT genotype (odds ratio = 1.6; 95% confidence interval, 1.1-2.4). In addition, among women, an inverse association was found between the variant A allele for a TNFSF5 6809G>A SNP and FL risk (OR = .61; 95% CI, 0.36-0.98). In genotype-phenotype studies, significantly reduced circulating soluble CD40 was observed in TNFRSF5 -1TT compared with -1CC carriers. Further, dendritic cells from those with -1TT versus -1CC genotypes exhibited lower CD40 cell surface expression. These results suggest that the TNFRSF5 -1C>T polymorphism may increase FL susceptibility through mechanisms that hinder cellular immune responses. Further studies are needed to explore these findings.
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PMID:A functional TNFRSF5 gene variant is associated with risk of lymphoma. 1828 17

Interaction between CD40 and its ligand, CD154, has a key function in immune regulation. Recent experimental data support a role of deregulated CD40 signalling in lymphomagenesis. Data from earlier studies that are part of this pooling study implicate a functional polymorphism (-1C>T, rs1883832) in the TNFRSF5 gene encoding CD40 in the etiology of follicular lymphoma. Here, the association of this variant with non-Hodgkin lymphoma (NHL) risk was replicated in a European multicenter study of 855 NHL cases and 1,206 controls. In the combined analysis of 2,617 cases and 3,605 controls, carrying the TT genotype was associated with an increased risk for all NHL (OR = 1.4; p for linear trend = 0.00009), diffuse large B-cell lymphoma (OR = 1.6; p for linear trend = 0.002) and follicular lymphoma (OR = 1.6; p for linear trend = 0.001). These data suggest a possible role of this functional polymorphism in lymphomas originating within the germinal center.
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PMID:A functional TNFRSF5 polymorphism and risk of non-Hodgkin lymphoma, a pooled analysis. 2047 10