SNPs in genes encoding for IL-10, TNF-α, and NFκB p105/p50 are associated with clinical prognostic factors for patients with Hodgkin lymphoma

PLoS One. 2021 Mar 8;16(3):e0248259. doi: 10.1371/journal.pone.0248259. eCollection 2021.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Genotype
  • Hodgkin Disease / diagnosis
  • Hodgkin Disease / genetics*
  • Humans
  • Interleukin-10 / genetics*
  • Male
  • Middle Aged
  • NF-kappa B p50 Subunit / genetics*
  • Neoplasm Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Promoter Regions, Genetic*
  • Retrospective Studies
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • IL10 protein, human
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • Neoplasm Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10

Grant support

This study was partially funded with research grants awarded to DEO by the São Paulo Research Foundation – FAPESP (grant number 2006/00591-5 / www.fapesp.br) and the State University of Sao Paulo (UNESP - www.unesp.br). RDG had scholarship awarded by the Brazilian Coordination for the Improvement of Higher Education Personnel – CAPES (grant number BEX: 9370/12-9 / www.capes.gov.br). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.