SNPs in genes encoding for IL-10, TNF-α, and NFκB p105/p50 are associated with clinical prognostic factors for patients with Hodgkin lymphoma
Open Access
- 8 March 2021
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 16 (3), e0248259
- https://doi.org/10.1371/journal.pone.0248259
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.Funding Information
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2006/00591-5)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (BEX: 9370/12-9)
This publication has 80 references indexed in Scilit:
- The Function of IntronsFrontiers in Genetics, 2012
- Hodgkin disease risk: Role of genetic polymorphisms and gene–gene interactions in inflammation pathway genesMolecular Carcinogenesis, 2010
- The classical Hodgkin's lymphoma microenvironment and its role in promoting tumour growth and immune escapeThe Journal of Pathology, 2010
- Mutations of NFKBIA in biopsy specimens from Hodgkin lymphomaCancer Genetics and Cytogenetics, 2010
- Polymorphic Variation in NFKB1 and Other Aspirin-Related Genes and Risk of Hodgkin LymphomaCancer Epidemiology, Biomarkers & Prevention, 2009
- Single nucleotide polymorphisms of tumor necrosis factor‐α and the susceptibility to bronchopulmonary dysplasiaPediatric Pulmonology, 2006
- Polymorphic haplotypes of the interleukin-10 5? flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritisArthritis & Rheumatism, 1999
- A Prognostic Score for Advanced Hodgkin's DiseaseThe New England Journal of Medicine, 1998
- Tissue microarrays for high-throughput molecular profiling of tumor specimensNature Medicine, 1998
- Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein.JCI Insight, 1994