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<p>Chronic hepatic inflammation, driven by factors including viral hepatitis and metabolic dysfunction, is a well-established precursor to hepatocellular carcinoma (HCC). The paper aimed to explore the concerted effects of germline polymorphisms in pivotal cytokine genes and their consequent impact on systemic and local inflammatory profiles in HCC pathogenesis. We conducted a hospital-based, retrospective case-control study involving the newly histologically confirmed primary HCC and age- and gender-matched healthy controls. Circulating levels of IL-1β, IL-6, IL-10 and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). Functional single nucleotide polymorphisms in the regulatory regions of their genes were genotyped via PCR- restricted fragment length polymorphism (PCR-RFLP) method. 160 patients and 280 healthy controls were enrolled. HCC patients exhibited significantly elevated serum concentrations of IL-1β, IL-6, IL-10 and TNF-α (all <i>p</i> &lt; 0.05) (mean age: 63.2 ± 7.8 years for cases; 64.0 ± 8.2 years for controls; male ratio: 68.1% for cases, 69.6% for controls). Key circulating cytokine levels were as follows: median IL-1β: 7.5 pg/mL for cases vs. 4.2 pg/mL for controls; IL-6: 18.5 pg/mL for cases vs. 11.3 pg/mL for controls; IL-10: 24.5 pg/mL for cases vs. 19.3 pg/mL for controls; TNF-α: 29.1 pg/mL for cases vs. 21.3 pg/mL for controls. IL-1β -511&#xa0;C/T, IL-10 -1082 G/A and TNF-α-308 G/A polymorphisms were associated with a significantly increased risk of HCC (all <i>p</i> &lt; 0.05). The frequencies of significant genetic variants were as follows: IL-1β -511 TT genotype: 62.5% in cases vs. 50.3% in controls; adjusted OR = 3.01, 95% CI: 1.65–5.50); IL-10 -1082 G/A AA genotype: 30.0% in cases vs.22.9% in controls; adjusted OR = 2.55, 95% CI: 1.47–4.43; TNF-α -308 G/A AA genotype: 26.8% in cases vs.23.2% in controls; adjusted OR = 1.76, 95% CI: 1.03–3.01. Functional polymorphisms in IL-1β and IL-10 are associated with HCC risk in this Chinese cohort. However, given the cross-sectional design, causal inference cannot be made. Larger prospective studies are needed to validate these findings and clarify the temporal relationship between cytokine dysregulation and HCC development.</p>

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IL‑1β, IL‑10, and TNF‑α gene polymorphisms are associated with cytokine levels and hepatocellular carcinoma risk in a Chinese cohort

  • 期刊论文

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  • 发表日期：

    2026年6月14日

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  • Xiang Yan,
  • Hulin Chang,
  • Jun Hai,
  • Zhiyong Zhang,
  • Yu Zhang,
  • Wei Zheng

摘要

Chronic hepatic inflammation, driven by factors including viral hepatitis and metabolic dysfunction, is a well-established precursor to hepatocellular carcinoma (HCC). The paper aimed to explore the concerted effects of germline polymorphisms in pivotal cytokine genes and their consequent impact on systemic and local inflammatory profiles in HCC pathogenesis. We conducted a hospital-based, retrospective case-control study involving the newly histologically confirmed primary HCC and age- and gender-matched healthy controls. Circulating levels of IL-1β, IL-6, IL-10 and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). Functional single nucleotide polymorphisms in the regulatory regions of their genes were genotyped via PCR- restricted fragment length polymorphism (PCR-RFLP) method. 160 patients and 280 healthy controls were enrolled. HCC patients exhibited significantly elevated serum concentrations of IL-1β, IL-6, IL-10 and TNF-α (all p < 0.05) (mean age: 63.2 ± 7.8 years for cases; 64.0 ± 8.2 years for controls; male ratio: 68.1% for cases, 69.6% for controls). Key circulating cytokine levels were as follows: median IL-1β: 7.5 pg/mL for cases vs. 4.2 pg/mL for controls; IL-6: 18.5 pg/mL for cases vs. 11.3 pg/mL for controls; IL-10: 24.5 pg/mL for cases vs. 19.3 pg/mL for controls; TNF-α: 29.1 pg/mL for cases vs. 21.3 pg/mL for controls. IL-1β -511 C/T, IL-10 -1082 G/A and TNF-α-308 G/A polymorphisms were associated with a significantly increased risk of HCC (all p < 0.05). The frequencies of significant genetic variants were as follows: IL-1β -511 TT genotype: 62.5% in cases vs. 50.3% in controls; adjusted OR = 3.01, 95% CI: 1.65–5.50); IL-10 -1082 G/A AA genotype: 30.0% in cases vs.22.9% in controls; adjusted OR = 2.55, 95% CI: 1.47–4.43; TNF-α -308 G/A AA genotype: 26.8% in cases vs.23.2% in controls; adjusted OR = 1.76, 95% CI: 1.03–3.01. Functional polymorphisms in IL-1β and IL-10 are associated with HCC risk in this Chinese cohort. However, given the cross-sectional design, causal inference cannot be made. Larger prospective studies are needed to validate these findings and clarify the temporal relationship between cytokine dysregulation and HCC development.