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Background <p>Hepatocellular carcinoma (HCC) represents a major global health burden, with chronic hepatitis B virus (HBV) infection being its predominant cause. However, only a fraction of chronic HBV carriers progress to HCC, suggesting a critical role for host genetic susceptibility. Interleukin-21 (IL-21) is a key immunomodulatory cytokine implicated in anti-tumor immunity, yet the association between IL-21 gene polymorphisms and HBV-related HCC risk remains unexplored. This study aimed to investigate the potential link between specific IL-21 single nucleotide polymorphisms (SNPs) and susceptibility to HBV-related HCC in a Chinese population. </p> Methods <p>A hospital-based case-control study was conducted involving 320 patients with HBV-related HCC and 560 age- and sex-matched healthy controls. Three IL-21 SNPs (rs2221903, rs907715, and rs12508721) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.</p> Results <p>Significant associations with HBV-related HCC susceptibility were identified for rs12508721 and rs2221903 (<i>P</i> &lt; 0.05), while no significant association was found for rs907715. The specific risk or protective genotypes and their corresponding ORs are detailed in the full text.</p> Conclusion <p>This study provides preliminary evidence that genetic polymorphisms in the IL-21 gene (rs12508721 and rs2221903) may be associated with susceptibility to HBV-related HCC. These findings suggest a potential role for host genetic variation in IL-21 in influencing outcomes following chronic HBV infection, although functional validation and replication in larger, independent cohorts are required to confirm these observations.</p>

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The effect of interleukin-21 on HBV-related hepatocellular carcinoma, from the perspective of genetics

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月16日

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  • Xi Wang,
  • Yanping Yao,
  • Xu Chen,
  • Jun Qiu,
  • Hailong Fu

摘要

Background

Hepatocellular carcinoma (HCC) represents a major global health burden, with chronic hepatitis B virus (HBV) infection being its predominant cause. However, only a fraction of chronic HBV carriers progress to HCC, suggesting a critical role for host genetic susceptibility. Interleukin-21 (IL-21) is a key immunomodulatory cytokine implicated in anti-tumor immunity, yet the association between IL-21 gene polymorphisms and HBV-related HCC risk remains unexplored. This study aimed to investigate the potential link between specific IL-21 single nucleotide polymorphisms (SNPs) and susceptibility to HBV-related HCC in a Chinese population.

Methods

A hospital-based case-control study was conducted involving 320 patients with HBV-related HCC and 560 age- and sex-matched healthy controls. Three IL-21 SNPs (rs2221903, rs907715, and rs12508721) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results

Significant associations with HBV-related HCC susceptibility were identified for rs12508721 and rs2221903 (P < 0.05), while no significant association was found for rs907715. The specific risk or protective genotypes and their corresponding ORs are detailed in the full text.

Conclusion

This study provides preliminary evidence that genetic polymorphisms in the IL-21 gene (rs12508721 and rs2221903) may be associated with susceptibility to HBV-related HCC. These findings suggest a potential role for host genetic variation in IL-21 in influencing outcomes following chronic HBV infection, although functional validation and replication in larger, independent cohorts are required to confirm these observations.