Association of TNF-α, TGF-β1, IFN-γ, IL-6, and IL-10 Gene Polymorphisms with Hodgkin Lymphoma: Susceptibility and Clinical Outcomes.

Background: In Hodgkin lymphoma (HL), cytokine-related genetic variation may influence disease susceptibility and clinical outcomes. This study investigated polymorphisms in tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1), interferon-gamma (IFN-γ), interleukin-6 (IL-6), and interleukin-10 (IL-10) in relation to HL susceptibility and progression-free survival (PFS). Methods: Seventy patients with HL and 70 healthy controls were included. Cytokine gene polymorphisms were analyzed from peripheral blood using sequence-specific primer polymerase chain reaction (PCR-SSP). Multiple comparisons were controlled using the Benjamini-Hochberg false discovery rate (FDR), and prognostic associations were evaluated using Firth penalized Cox regression. Results: Several genotype-level associations were nominally significant before multiple-testing correction, including TNF-α (-308) GA, IFN-γ (+874) TT, IL-6 (-174) GG, TGF-β1 codon 10 TT, IL-10 (-1082) GG, IL-10 (-819) CC, and IL-10 (-592) CC genotypes. In addition, selected TGF-β1 and IL-10 predefined multilocus genotype combinations showed nominal associations with HL susceptibility. However, none of these genotype-level or multilocus genotype-combination associations remained statistically significant after FDR correction. In contrast, significant allele-level associations persisted after FDR adjustment for the IL-6 (-174) G allele, TGF-β1 codon 10 T allele, and IL-10 (-1082) G, IL-10 (-819) C, and IL-10 (-592) C alleles. Bone marrow involvement remained associated with inferior PFS (HR = 11.62, 95% confidence interval (CI): 3.61-34.66; p < 0.001), although the wide CI warrants cautious interpretation. The IL-6 (-174) CC genotype also showed an association with inferior PFS (HR = 7.09, 95% CI: 1.34-25.29; p = 0.025); however, this estimate was based on only two carriers and should be considered exploratory. Conclusions: Selected cytokine gene variants, particularly at the allele level, may be associated with HL susceptibility. The prognostic association of IL-6 (-174) CC requires confirmation in larger cohorts.