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IL-23R polymorphisms, HBV infection, and risk of hepatocellular carcinoma in a high-risk Chinese population

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

The interleukin-23 receptor (IL-23R) plays an important role in the T-helper 17 cell-mediated inflammatory process and is also involved in tumor immune surveillance, which may be linked to carcinogenesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). In this study, we hypothesized that potentially functional genetic variants of the IL-23R gene may modify HCC risk.

Methods

We genotyped two single-nucleotide polymorphisms (SNPs) of IL-23R, rs6682925 and rs1884444, in a case–control study of 837 HCC cases, 899 HBV surface antigen (HBsAg)-positive controls, and 743 HBsAg-negative controls. A reporter gene assay was performed to evaluate the functional relevance of the rs6682925 SNP located at the promoter region of the IL-23R gene.

Results

We found that the two SNPs were associated with the risk of HCC when compared with both the HBsAg-positive and -negative controls. When compared with all controls, IL-23R rs6682925 and rs1884444 both increased the HCC risk in a recessive genetic model [rs6682925 CC vs. TT/TC: odds ratio (OR) 1.35, 95 % confidence interval (CI) 1.07–1.70; rs1884444 GG vs. TT/TG: OR 1.36, 95 % CI 1.05–1.77]. Furthermore, the variant C allele of rs6682925 in the promoter region of IL-23R was associated with increased reporter gene activity.

Conclusions

These findings indicate that genetic variants in IL-23R may contribute to HCC development.

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Acknowledgments

This work was supported in part by the National Natural Science Foundation of China (Grant Nos. 30800946, 81072344), a Grant from the Health Bureau of Jiangsu Province I, Jiangsu 333 program (Grant No. DG216D5023), and the Priority Academic Program Development of Jiangsu Higher Education Institutions, Foundation for the Author of National Excellent Doctoral Dissertation (Grant No. 201081).

Conflict of interest

None declared.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 140 Hanzhong Rd., Nanjing, 210029, China

    Yan Xu, Yao Liu, Shandong Pan, Hongbing Shen & Zhibin Hu

  2. Department of Hepatobiliary Surgery, Nantong Tumor Hospital, Nantong, 226361, China

    Li Liu & Jibin Liu

  3. Department of Infection Diseases, Jiangsu Province Center for Disease Prevention and Control, Nanjing, 210009, China

    Xiangjun Zhai

  4. Section of Clinical Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, 210029, China

    Hongbing Shen & Zhibin Hu

Authors
  1. Yan Xu
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  2. Yao Liu
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  3. Shandong Pan
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  4. Li Liu
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  5. Jibin Liu
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Corresponding author

Correspondence to Zhibin Hu.

Additional information

Y. Xu and Y. Liu contributed equally to this work.

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Xu, Y., Liu, Y., Pan, S. et al. IL-23R polymorphisms, HBV infection, and risk of hepatocellular carcinoma in a high-risk Chinese population. J Gastroenterol 48, 125–131 (2013). https://doi.org/10.1007/s00535-012-0620-1

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  • DOI: https://doi.org/10.1007/s00535-012-0620-1

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