Association of Common Polymorphisms in the Interleukin-1 Beta Gene with Hepatocellular Carcinoma in Caucasian Patients with Chronic Hepatitis B

doi:10.3390/pathogens12010054

. 2022 Dec 29;12(1):54.

doi: 10.3390/pathogens12010054.

Association of Common Polymorphisms in the Interleukin-1 Beta Gene with Hepatocellular Carcinoma in Caucasian Patients with Chronic Hepatitis B

Affiliations

¹ Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103 Leipzig, Germany.
² Hepatogastroenterology Unit, Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, "Attikon" University General Hospital, 12462 Athens, Greece.
³ Department of Medicine-Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, 14197 Berlin, Germany.
⁴ Department of Gastroenterology, Kantonsspital Baselland, 4410 Liestal, Switzerland.
⁵ Liver and Study Center Checkpoint, 10969 Berlin, Germany.
⁶ Storr Liver Centre, Westmead Hospital and Westmead Millennium Institute for Medical Research, University Sydney, Sydney 2006, Australia.
⁷ Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, 60528 Frankfurt, Germany.
⁸ Center for Hematology and Oncology Bethanien, 60389 Frankfurt, Germany.

PMID: 36678401
PMCID: PMC9861021
DOI: 10.3390/pathogens12010054

Association of Common Polymorphisms in the Interleukin-1 Beta Gene with Hepatocellular Carcinoma in Caucasian Patients with Chronic Hepatitis B

Janett Fischer et al. Pathogens. 2022.

. 2022 Dec 29;12(1):54.

doi: 10.3390/pathogens12010054.

Authors

Affiliations

¹ Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103 Leipzig, Germany.
² Hepatogastroenterology Unit, Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, "Attikon" University General Hospital, 12462 Athens, Greece.
³ Department of Medicine-Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, 14197 Berlin, Germany.
⁴ Department of Gastroenterology, Kantonsspital Baselland, 4410 Liestal, Switzerland.
⁵ Liver and Study Center Checkpoint, 10969 Berlin, Germany.
⁶ Storr Liver Centre, Westmead Hospital and Westmead Millennium Institute for Medical Research, University Sydney, Sydney 2006, Australia.
⁷ Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, 60528 Frankfurt, Germany.
⁸ Center for Hematology and Oncology Bethanien, 60389 Frankfurt, Germany.

PMID: 36678401
PMCID: PMC9861021
DOI: 10.3390/pathogens12010054

Abstract

Interleukin-1 beta (IL-1β) promotes liver disease progression and hepatocarcinogenesis in chronic hepatitis B (CHB). Single nucleotide polymorphisms (SNPs) within the promotor region of the IL-1β gene can affect the progression towards liver cirrhosis and hepatocellular carcinoma (HCC). Aims: We aimed to investigate the association of three common IL-1β SNPs with hepatitis B virus (HBV)-related HCC in Caucasian patients. Method: A Caucasian cohort of 99 patients with HBe antigen (Ag)-positive CHB, 255 patients with HBeAg-negative CHB and 278 inactive carriers (IC) were enrolled. 105 patients were diagnosed with liver cirrhosis, and 64 with HCC and cirrhosis. Genotyping of the IL-1β rs1143623, rs1143627 and rs16944 was performed. Results: The rs1143627 TT and rs16944 CC genotypes were more frequent in patients with HCC compared to patients without liver tumours (48% vs. 33%, p = 0.018 and 47% vs. 31%, p = 0.001, respectively). In multivariate analysis, the rs16944 CC genotype was independently associated with HCC (OR = 6.44 [95% CI 1.50-27.59] p = 0.012). The haplotype, including rs1143623 TT and rs16944 CC, was a risk factor for HCC development (OR = 1.55 [95% CI 1.04-2.32] p = 0.031). Conclusions: We identified an association of common IL-1β SNPs with HBV-related HCC in a Caucasian population. The effect was independent of the phases of chronic HBV infection, which are currently regarded as important HCC risk factors.

Keywords: liver cancer; proinflammatory cytokine; risk variant.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Serum levels of interleukin (IL) 1β in patients with chronic HBV infection and healthy controls (HC) stratified according to the *IL-1β* (A) rs1143627 and (B) rs16944 genotypes. Statistical analysis was performed with Mann–Whitney U Test. Columns show mean values with bars indicating standard error of mean. Y-axis is shown in log10.

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This study was supported by a research grant from GILEAD Sciences GmbH.

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[1] Galle P.R., Forner A., Llovet J.M., Mazzaferro V., Piscaglia F., Raoul J.L., Schirmacher P., Vilgrain V., European Association for the Study of the Liver EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J. Hepatol. 2018;69:182–236. doi: 10.1016/j.jhep.2018.03.019. - DOI - PubMed

[2] Galle P.R., Forner A., Llovet J.M., Mazzaferro V., Piscaglia F., Raoul J.L., Schirmacher P., Vilgrain V., European Association for the Study of the Liver EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J. Hepatol. 2018;69:182–236. doi: 10.1016/j.jhep.2018.03.019. - DOI - PubMed

[3] European Association for the Study of the Liver EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J. Hepatol. 2017;67:370–398. doi: 10.1016/j.jhep.2017.03.021. - DOI - PubMed

[4] European Association for the Study of the Liver EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J. Hepatol. 2017;67:370–398. doi: 10.1016/j.jhep.2017.03.021. - DOI - PubMed

[5] Raffetti E., Fattovich G., Donato F. Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: A systematic review and meta-analysis. Liver Int. 2016;36:1239–1251. doi: 10.1111/liv.13142. - DOI - PubMed

[6] Raffetti E., Fattovich G., Donato F. Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: A systematic review and meta-analysis. Liver Int. 2016;36:1239–1251. doi: 10.1111/liv.13142. - DOI - PubMed

[7] Dondeti M.F., El-Maadawy E.A., Talaat R.M. Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms. World J. Gastroenterol. 2016;22:6800–6816. doi: 10.3748/wjg.v22.i30.6800. - DOI - PMC - PubMed

[8] Dondeti M.F., El-Maadawy E.A., Talaat R.M. Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms. World J. Gastroenterol. 2016;22:6800–6816. doi: 10.3748/wjg.v22.i30.6800. - DOI - PMC - PubMed

[9] He D., Tao S., Guo S., Li M., Wu J., Huang H., Guo X., Yan G., Zhu P., Wang Y. Interaction of TLR-IFN and HLA polymorphisms on susceptibility of chronic HBV infection in Southwest Han Chinese. Liver Int. 2015;35:1941–1949. doi: 10.1111/liv.12756. - DOI - PMC - PubMed

[10] He D., Tao S., Guo S., Li M., Wu J., Huang H., Guo X., Yan G., Zhu P., Wang Y. Interaction of TLR-IFN and HLA polymorphisms on susceptibility of chronic HBV infection in Southwest Han Chinese. Liver Int. 2015;35:1941–1949. doi: 10.1111/liv.12756. - DOI - PMC - PubMed

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Association of Common Polymorphisms in the Interleukin-1 Beta Gene with Hepatocellular Carcinoma in Caucasian Patients with Chronic Hepatitis B

Affiliations

Association of Common Polymorphisms in the Interleukin-1 Beta Gene with Hepatocellular Carcinoma in Caucasian Patients with Chronic Hepatitis B

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

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References

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Abstract

Conflict of interest statement

Figures

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References

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