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.
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-23Rrs6682925 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.
Authors: Richard H Duerr; Kent D Taylor; Steven R Brant; John D Rioux; Mark S Silverberg; Mark J Daly; A Hillary Steinhart; Clara Abraham; Miguel Regueiro; Anne Griffiths; Themistocles Dassopoulos; Alain Bitton; Huiying Yang; Stephan Targan; Lisa Wu Datta; Emily O Kistner; L Philip Schumm; Annette T Lee; Peter K Gregersen; M Michael Barmada; Jerome I Rotter; Dan L Nicolae; Judy H Cho Journal: Science Date: 2006-10-26 Impact factor: 47.728
Authors: M Barajas; G Mazzolini; G Genové; R Bilbao; I Narvaiza; V Schmitz; B Sangro; I Melero; C Qian; J Prieto Journal: Hepatology Date: 2001-01 Impact factor: 17.425
Authors: H Kuper; A Tzonou; E Kaklamani; C C Hsieh; P Lagiou; H O Adami; D Trichopoulos; S O Stuver Journal: Int J Cancer Date: 2000-02-15 Impact factor: 7.396
Authors: Anne-Marie Baird; Eilis Dockry; Anne Daly; Emma Stack; Derek G Doherty; Kenneth J O'Byrne; Steven G Gray Journal: Front Oncol Date: 2013-06-19 Impact factor: 6.244