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


METHODS
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.


RESULTS
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.


CONCLUSIONS
These findings indicate that genetic variants in IL-23R may contribute to HCC development.
Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 140 Hanzhong Rd., Nanjing, 210029, China.
Yan
Y
Xu
Yao
Y
Liu
Shandong
S
Pan
Li
L
Liu
Jibin
J
Liu
Xiangjun
X
Zhai
Hongbing
H
Shen
Zhibin
Z
Hu
D044466:Asian People / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D002681:China; D016001:Confidence Intervals; D005260:Female; D017930:Genes, Reporter; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018123:Receptors, Interleukin / Q000235:genetics*
D006514:Hepatitis B Surface Antigens; C515500:IL23R protein, human; D018123:Receptors, Interleukin