Genetic variants of interleukin 1 beta are associated with viral hepatitis-related HCC in Caucasian patients

Background The proinflammatory cytokine interleukin 1 beta (IL-1b) mediates several immune responses and promotes the development of liver cirrhosis and hepatocellular carcinoma (HCC). Alterations in the IL-1b gene can affect cytokine expression and signaling and can augment the progression of liver disease towards more severe stages. We aimed to investigate the association of polymorphisms within the promotor region of the IL-1b gene with liver disease progression in Caucasian patients related to chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV).

Method In this retrospective study, 632 Caucasian patients with chronic HBV infection, of whom 105 patients were diagnosed with liver cirrhosis and 64 with liver cirrhosis and HCC, 101 Caucasian patients with chronic HCV infection and HCC and 124 matched HCV controls without HCC were enrolled. Host genomic DNA was extracted from peripheral blood samples. Genotyping of IL-1b polymorphisms rs1143623, rs1146327 and rs16944 was performed.

Results The frequencies of Il-1b rs1146327 TT and rs16944 CC were higher in patients with HBV-related HCC than in patients without HCC (rs1146327 TT: 48 % vs. 33 %, p=0.018, rs16944 CC: 47 % vs. 31 %, p=0.001). The same was true in patients with HCV-related HCC and the matched controls without HCC (rs1146327 TT: 53 % vs. 39 %, p=0.032, rs16944 CC: 53 % vs. 40 %, p=0.031). In multivariate analysis, only the IL-1b rs16944 CC genotype remained independently associated with HCC in patients with chronic HBV infection (OR=3.78 [95 % CI: 1.08-13.27] p=0.038) and in patients with chronic HCV infection (OR=1.80 [95 % CI: 1.01-3.21] p=0.048). In haplotype analysis, the haplotype including both variants rs1143627 TT and rs16944 CC was a risk factor for the development of HBV-related HCC (OR=1.55 [95 % CI: 1.04-2.32] p=0.033) and HCV-related HCC (OR=1.66 [95 % CI: 1.09-2.53] p=0.017).

Conclusions We identified an association of common IL-1b polymorphisms with the presence of HBV- and HCV-related HCC in a Caucasian population. It seems that the alterations within the IL-1b gene are shared risk factors for the development of HCC related to viral hepatitis. Further studies in larger cohorts and functional analyses are required to confirm the results and to elucidate the role of the risk loci in liver fibrogenesis and carcinogenesis.

Publication History

Article published online:
04 January 2021