Abstract
Classical Hodgkin lymphoma (cHL) is a B-cell-derived malignant neoplasia that has a unique histological distribution, in which the scarce malignant Hodgkin and Reed-Sternberg cells are surrounded by nonmalignant inflammatory cells. The interactions between the malignant and inflammatory cells are mediated by aberrantly produced cytokines, which play an important role in tumor immunopathogenesis. Single nucleotide polymorphisms (SNPs) in genes encoding cytokines and their regulatory proteins may influence the peripheral levels of these molecules and affect disease’s pathobiology. In this study, we evaluate SNPs in the promoter regions of the genes encoding for two key cytokines in Hodgkin lymphoma: IL-10 (SNP/pIL10–592, rs1800872; and SNP/pIL10–1082, rs1800896) and TNF-α (SNP/pTNF -238, rs361525; and SNP/pTNF -862, rs1800630), as well as an SNP in the intronic region of the NFκB1 gene (SNP/iNFKB1, rs1585215), an important regulator of cytokine gene expression. We then look to their possible association with clinical and laboratory features in cHL patients. Seventy-three patients with cHL are genotyped by qPCR-high resolution melting. The SNPs’ genotypes are analyzed individually for each SNP, and when more than two allelic combinations are identified, the genotypes are also divided into two groups according to proposed biological relevance. By univariate analysis, patients harboring SNP/pTNF -238 AG genotype more frequently have EBV-associated cHL compared to homozygous GG, whereas the presence of mediastinal disease (bulky and nonbulky) is more common in the pIL10–592 AC/CC group compared to the AA homozygous group. Patients with SNP/iNFKB1 AA genotype more frequently have stage IV and extranodal disease at diagnosis. These results indicate that some SNPs’ genotypes for IL-10 and TNF-α genes are associated with prognostic parameters in cHL. For the first time, the SNP/iNFKB1 is described in association with clinical features of the disease.
Highlights
Hodgkin lymphoma (HL) is a B-cell-derived malignant neoplasia that accounts for approximately 10% of all human lymphomas
High serum levels of TNF-α were associated with clinical features and poorer prognosis in classical form of HL (cHL) [28], data on the role of Single nucleotide polymorphisms (SNPs) in the TNF gene in cHL are scarce
Considering that Epstein-Barr virus (EBV) is more frequently observed in older cHL patients and MC subtype [60], the multivariate analysis was adjusted for age and histologic subtype
Summary
Hodgkin lymphoma (HL) is a B-cell-derived malignant neoplasia that accounts for approximately 10% of all human lymphomas. The disease has a unique histological appearance in which the neoplastic component—the Hodgkin and Reed-Sternberg cells (H-RS)—is scarce, and tumors are mostly formed by nonmalignant inflammatory cells [1, 2]. Prognostic models based on clinical and laboratory parameters for cHL are useful in clinical practice [8,9,10], they may not consider the disease pathobiology, which may account for their unsatisfactory performance for treatment stratification. Data on new putative prognostic factors to accurately predict cHL behavior and outcomes are of major interest in the clinical setting
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