IL-23R polymorphisms, HBV infection, and risk of hepatocellular carcinoma in a high-risk Chinese population
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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.
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.
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.
These findings indicate that genetic variants in IL-23R may contribute to HCC development.
KeywordsInterleukin-23 receptor Polymorphism Hepatocellular carcinoma HBV Reporter gene
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
- 1.Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB. Cancer incidence in five continents. Vol. VIII. IARC Scientific Publications No. 155, Lyon, IARC. 2002. p.1–781.Google Scholar