title: Association of transforming growth factor-beta1 gene polymorphisms with a hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection.
abstract: Transforming growth factor-beta1 (TGF-beta1) can act as both a tumor suppressor and a stimulator of tumor progression. We have examined the relationship between polymorphisms of the TGF-beta1 gene and the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection. A total of 1,237 Korean subjects were prospectively enrolled; 1,046 patients with chronic HBV infection and 191 healthy controls with no evidence of recent or remote HBV infection. The patients were divided into two groups: those without (n = 809) and those with HCC (n = 237). Single nucleotide polymorphisms (SNPs) of TGF-beta1 were searched for and genotyped using the single base extension method. In Korean subjects, only two SNPs were found among the seven known polymorphisms of TGF-beta1, at position -509 and in codon 10. The risk of HCC was significantly lower in patients with the T/T or C/T genotypes than in those with the C/C genotypes at position -509 (P < 0.02), and also lower among those with the Pro/Pro or Leu/Pro genotypes than in those with the Leu/Leu genotypes in codon 10 (P < 0.007). Haplotype analysis revealed that the possession of [-509C > T; L10P] conferred a decreased likelihood of HCC (OR = 0.74; 95% CI, 0.59-0.93; P = 0.008). In conclusion, the presence of the TGF-beta1 -509C > T promoter or of the L10P polymorphism, and the combination of both [-509C > T; L10P] as a haplotype were strongly associated with a reduced risk of HCC in patients with chronic HBV infection.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Korea.
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Jong Pil
authors.initials: JP
authors.lastname: Im
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Min
authors.forename: Hyun-Dae
authors.initials: HD
authors.lastname: Kim
authors.forename: Ji Bong
authors.initials: JB
authors.lastname: Jeong
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Chung Yong
authors.initials: CY
authors.lastname: Kim
authors.forename: Myung Soo
authors.initials: MS
authors.lastname: Kim
authors.forename: Jun Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Jung
authors.forename: Lyoung Hyo
authors.initials: LH
authors.lastname: Kim
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006509:Hepatitis B / Q000150:complications / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
chemical_list: C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1