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

<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>These findings indicate that genetic variants in IL-23R may contribute to HCC development. [ABSTRACT FROM AUTHOR]