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Association of IL-1β (-511 C/T) Polymorphism with Elevated Serum IL-1β Levels and Hepatocellular Carcinoma Risk in HCV-Infected Patients

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Abstract

Background

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, frequently linked to chronic Hepatitis C virus (HCV) infection. Interleukin-1β (IL-1β), a pro-inflammatory cytokine, mediates hepatic inflammation, stimulates neovascularization, and enhances tumor aggressiveness. Genetic variation in the IL-1β promoter region, particularly the -511 C/T polymorphism, has been proposed to influence susceptibility to HCC, though published data are conflicting.

Objective

This study aimed to evaluate the relationship between IL-1β (-511 C/T) polymorphism, circulating IL-1β concentrations, and the development of HCC among patients with chronic HCV infection.

Methods

Ninety volunteers were enrolled and categorized into three groups: 30 controls (Group I), 30 HCV + patients without HCC (Group II), and 30 HCV + with HCC patients (Group III). The IL-1β (-511 C/T) polymorphism was identified through PCR-based analysis, and circulating IL-1β levels were measured using enzyme-linked immunoassays.

Results

A significant increase in IL-1B (-511) T allele frequency in group II and III HCV patients than controls (n = 26 (43.5%), n = 39(65.5%), and n = 8(13.5%), respectively, P < 0.001), odds ratio (OR) = 4.97 (1.87- 13.61) and 12.07 (4.47- 33.7) (p < 0.05), respectively). C allele frequency was significantly lower in group II and group III than in controls (n = 34(56.5%), n = 21(34.5%), and n = 52 (86.5%), respectively, p < 0.001). IL-1β serum levels were significantly increased in patients compared to controls, with more increase in group III than group II (t = 13.69, P < 0.0001). TT and CT genotypes have increased IL-1β levels than CC carriers.

Conclusion

The IL-1β (-511 C/T) polymorphism is associated with elevated IL-1β levels, contributing to an increased risk of HCC in HCV-infected Egyptian patients.

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Data Availability

The analyzed data of the current study are available from the corresponding author upon reasonable request.

Code Availability

Not applicable.

Abbreviations

ALP :

Alkaline phosphatase.

AMA :

Anti-mitochondrial antibody

ANOVA :

Analysis of variance.

AST :

Aspartate transaminase.

Cis :

Confidence intervals.

COX -2 :

Cyclooxygenase.

ELISA :

Enzyme-linked immune assay.

GGT :

Gamma-glutamyl transferase.

HCC :

Hepatocellular carcinoma.

HCV :

Chronic Hepatitis C virus.

HWE :

Hardy-Weinberg equilibrium.

IL-1β :

Interleukin-1β.

KCs :

Kupffer cells.

ORs :

Odds ratios.

PBMCs :

Peripheral blood mononuclear cells.

PCR :

Polymerase Chain Reaction.

PCR-RFLP :

The polymerase chain reaction-restriction fragment length polymorphism.

SNPs :

Single Nucleotide Polymorphisms.

SPSS :

Statistical Package for the Social Sciences.

TNF-α :

Tumor necrosis factor-alpha.

α-AFP :

Alpha-fetoprotein

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Acknowledgements

The Researcher would like to thank the Deanship of Graduate Studies and Scientific Research at Qassim University for financial support (QU-APC-2025). In addition, the author would like to acknowledge Prof. Mohamad Badawi, the Internal Medicine consultant at Zagazig University Hospitals and Professor of Internal Medicine at the Faculty of Medicine at Zagazig University, Egypt, for his support and effort in determining patient criteria and sample collection. I would like to thank all the technical staff and patients involved in this study.

Funding

Not applicable.

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Authors and Affiliations

  1. Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, 51452, Saudi Arabia

    Amal Mohamad Husein Mackawy

  2. Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Zagazig University, Zagazig City, Egypt

    Amal Mohamad Husein Mackawy

Authors
  1. Amal Mohamad Husein Mackawy
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Contributions

Amal Mohamad Husein Mackawy (AMHM) The study design, collection of the patients&apos; samples; methodology lab analysis, and interpretation of the patient data regarding serum IL-1B levels and genetic polymorphism detection. Analysis of the data, writing the draft and final manuscript copies.

Corresponding author

Correspondence to Amal Mohamad Husein Mackawy.

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Ethics Approval

The research protocol received ethical clearance from the Faculty of Medicine Ethics Committee at Zagazig University (No # 1–6-2022).

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All participants provided written informed consent before enrollment, following a detailed explanation of the study's aims, methods, and possible outcomes.

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Written consent for study involvement and subsequent publication of data was obtained from every individual before participation.

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The authors declare no competing interests.

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Mackawy, A.M.H. Association of IL-1β (-511 C/T) Polymorphism with Elevated Serum IL-1β Levels and Hepatocellular Carcinoma Risk in HCV-Infected Patients. SN Compr. Clin. Med. 7, 301 (2025). https://doi.org/10.1007/s42399-025-02084-y

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