Open AccessAssociation between transforming growth factor-β1 -509 C>T variants and hepatocellular carcinoma susceptibility: a meta-analysis
Author(s) -
Nobuyuki Toshikuni,
Yasuhiro Matsue,
Takahiro Minato,
Nobuki Hayashi,
Mikihiro Tsutsumi
Publication year - 2016
Publication title -
neoplasma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.628
H-Index - 50
eISSN - 1338-4317
pISSN - 0028-2685
DOI - 10.4149/neo_2016_615
Subject(s) - hepatocellular carcinoma , odds ratio , medicine , hepatitis b virus , genotype , hepatitis c virus , meta analysis , case control study , liver disease , gastroenterology , genetic predisposition , transforming growth factor , genetic association , genetic model , hepatitis b , oncology , single nucleotide polymorphism , immunology , disease , virus , gene , biology , genetics
The transcriptional activity of transforming growth factor-β (TGF-β) is increased in subjects with hepatocellular carcinoma (HCC). Recent studies have indicated that the -509C genotype in hepatitis B virus (HBV)-infected subjects and the -509T genotype in hepatitis C virus (HCV)-infected subjects can increase the transcriptional activity of the TGF-β1 gene. We conducted a meta-analysis to clarify whether these two hepatitis viruses affect the association between TGF-β1 C-509T variants and HCC susceptibility. Using data derived from 8 case-control studies available in the PubMed database (5 with Asian and 3 with Caucasian populations), including 1,427 cases and 3,735 controls [1,610 patients with chronic liver disease and 2,125 healthy controls], we calculated pooled odds ratios with corresponding 95% confidence intervals. We used dominant (TT + CT vs. CC), recessive (TT vs. CC + CT), and co-dominant (TT vs. CC and CT vs. CC) genetic models. An overall analysis showed no association between the TGF-β1 C-509T variants and HCC susceptibility for all models. In contrast, a subgroup analysis, based on the infecting hepatitis viruses, provided the following results. Among the cases and controls with chronic liver disease, the TGF-β1 C-509T variants were significantly associated with decreased HCC susceptibility for two models with HBV-infected subjects, whereas the variants were significantly associated with increased HCC susceptibility for one model with HCV-infected subjects. Among the cases and healthy controls, there was a significant association between the TGF-β1 C-509T variants and increased HCC susceptibility for two models involving HCV-infected subjects. Among the cases and the entire control group, the same results were obtained for all genetic models with HCV-infected subjects. Although further data accumulation is required, our results suggest that these two hepatitis viruses affect the association between TGF-β1 C-509T variants and HCC susceptibility in opposite manners.