title: Polymorphisms in the potential functional regions of the TGF-β 1 and TGF-β receptor genes and disease susceptibility in HBV-related hepatocellular carcinoma patients.
abstract: Hepatocellular carcinoma (HCC) is a disease of multiple etiologies caused by the accumulation of genetic and epigenetic defects. Current evidence indicates that the transforming growth factor beta (TGF-β) signaling pathway has a significant impact on different cellular process. Members of the TGF-β superfamily (TGF-β1, the type I TGF-β receptor [TβRI], type II TGF-β receptor [TβRII], and type III TGF-β receptor]) play an important role in tumorigenesis. Numerous studies show that genetic polymorphisms in TGF-β superfamily genes are associated with HCC in East Asian populations. We studied 16 single nucleotide polymorphisms (SNPs) in four genes (TGF-β1, TβRI, TβRII, and TβRIII) to examine their associations with hepatocarcinogenesis. A total of 1228 Chinese Han participants were enrolled in the study (881 control participants who were negative for all hepatitis B virus [HBV] serum markers and 347 case participants with HBV-related HCC). Genotyping was conducted using the TaqMan method. The results showed that the frequency of the rs1805110 T allele was significantly higher in the case group than in the control group (P = 0.034). After stratification, the results for rs1805110 remained significant in male participants (P = 0.005), but there was no statistical difference in females. In males, the frequency of the C-C-G-C-A haplotype resulting from SNPs rs1805110, rs2810904, rs1805112, rs284878, and rs1804506 in TβRIII was significantly lower in the case group than in the control group (P = 0.001), whereas the reverse was true for the T-C-G-C-A haplotype (P = 0.036). We conclude that the rs1805110T allele is associated with susceptibility to HBV-related HCC in males.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, PR China.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Xin
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Aiqiang
authors.initials: A
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Yan
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Wu
authors.forename: Xilin
authors.initials: X
authors.lastname: Zhu
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006515:Hepatitis B virus / Q000472:pathogenicity*; D006801:Humans; D015810:Linkage Disequilibrium; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011509:Proteoglycans / Q000235:genetics*; D011897:Random Allocation; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C071736:betaglycan; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II