Association between the IL-35 rs583911 polymorphism and hepatocellular carcinoma risk in patients infected with chronic hepatitis B virus
- 1Department of Clinical Laboratory, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060 China
- 2Department of Clinical Laboratory, Tianjin Dongli Hospital, Tianjin, 300300 China
Abstract
Background: The immunoregulatory cytokine interleukin (IL)-35 has been implicated in the pathogenesis of hepatocellular carcinoma (HCC). Here, we explored the association between single-nucleotide polymorphisms (SNPs) in the IL-35 gene and the occurrence of HCC in patients with chronic hepatitis B virus (HBV).
Methods: We selected 39 patients with chronic hepatitis B (HBV) and 52 patients with HBV-related hepatocellular carcinoma (HCC) as the case groups, along with 42 healthy individuals as the control group. We genotyped five IL-35-related single-nucleotide polymorphisms (SNPs) and analyzed their association with HCC risk. In addition, serum IL-35 levels, lymphocyte counts, and regulatory T cell (Treg) frequencies were measured in peripheral blood across all groups.
Results: The frequency of the rs583911 AA genotype tended to increase from healthy controls (4.8%) to patients with chronic HBV (10.3%) to patients with HCC (21.2%) (P for trend = 0.03). When patients with HCC were compared to non-HCC controls (healthy controls + chronic HBV carriers), the rs583911 AA genotype was associated with HCC risk (OR = 3.35; 95% CI: 1.17–9.61, P = 0.020). After adjusting for age, sex, cirrhosis status, and antiviral therapy, the association was no longer statistically significant (adjusted P = 0.085). Serum IL-35 levels were significantly elevated in both the HBV and the HCC groups compared with those in the control group (P < 0.001), with no significant difference between the HBV and the HCC groups (P = 0.434). Within the HCC subgroup, patients with the AA genotype tended to have higher IL-35 levels (P = 0.047). Flow cytometry analysis of a subset of samples (6 controls, 6 patients with HBV, and 28 patients with HCC) revealed that the number of Treg cells was greater in patients with HCC than in those with HBV (P = 0.038).
Conclusion: Our findings suggest a potential association between the rs583911 AA genotype and HBV-related HCC risk. However, these exploratory findings did not remain statistically significant after rigorous adjustment for multiple comparisons and potential confounders; therefore, validation in larger, independent cohorts is needed.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16609-8.
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BibTeX
@article{dong2026association,
title = {{Association between the IL-35 rs583911 polymorphism and hepatocellular carcinoma risk in patients infected with chronic hepatitis B virus}},
author = {Hui Dong and Duo Zuo and Yuxuan Li and Zhengkun Zhu and Xia Sun and Wei Meng and Xuan Liu and Wantong Wu and Li Ren},
journal = {BMC Cancer},
year = {2026},
month = aug,
doi = {10.1186/s12885-026-16609-8},
url = {https://doi.org/10.1186/s12885-026-16609-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Association between the IL-35 rs583911 polymorphism and hepatocellular carcinoma risk in patients infected with chronic hepatitis B virus
AU - Hui Dong
AU - Duo Zuo
AU - Yuxuan Li
AU - Zhengkun Zhu
AU - Xia Sun
AU - Wei Meng
AU - Xuan Liu
AU - Wantong Wu
AU - Li Ren
PY - 2026
DA - 2026/08/10
JO - BMC Cancer
DO - 10.1186/s12885-026-16609-8
UR - https://doi.org/10.1186/s12885-026-16609-8
AB - Background: The immunoregulatory cytokine interleukin (IL)-35 has been implicated in the pathogenesis of hepatocellular carcinoma (HCC). Here, we explored the association between single-nucleotide polymorphisms (SNPs) in the IL-35 gene and the occurrence of HCC in patients with chronic hepatitis B virus (HBV). Methods: We selected 39 patients with chronic hepatitis B (HBV) and 52 patients with HBV-related hepatocellular carcinoma (HCC) as the case groups, along with 42 healthy individuals as the control group. We genotyped five IL-35-related single-nucleotide polymorphisms (SNPs) and analyzed their association with HCC risk. In addition, serum IL-35 levels, lymphocyte counts, and regulatory T cell (Treg) frequencies were measured in peripheral blood across all groups. Results: The frequency of the rs583911 AA genotype tended to increase from healthy controls (4.8%) to patients with chronic HBV (10.3%) to patients with HCC (21.2%) (P for trend = 0.03). When patients with HCC were compared to non-HCC controls (healthy controls + chronic HBV carriers), the rs583911 AA genotype was associated with HCC risk (OR = 3.35; 95% CI: 1.17–9.61, P = 0.020). After adjusting for age, sex, cirrhosis status, and antiviral therapy, the association was no longer statistically significant (adjusted P = 0.085). Serum IL-35 levels were significantly elevated in both the HBV and the HCC groups compared with those in the control group (P < 0.001), with no significant difference between the HBV and the HCC groups (P = 0.434). Within the HCC subgroup, patients with the AA genotype tended to have higher IL-35 levels (P = 0.047). Flow cytometry analysis of a subset of samples (6 controls, 6 patients with HBV, and 28 patients with HCC) revealed that the number of Treg cells was greater in patients with HCC than in those with HBV (P = 0.038). Conclusion: Our findings suggest a potential association between the rs583911 AA genotype and HBV-related HCC risk. However, these exploratory findings did not remain statistically significant after rigorous adjustment for multiple comparisons and potential confounders; therefore, validation in larger, independent cohorts is needed. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16609-8.
SN - 1471-2407
ER -