Association of transforming growth factor-β1 gene polymorphisms with a hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection (original) (raw)

Abstract

Transforming growth factor-β1 (TGF-β1) can act as both a tumor suppressor and a stimulator of tumor progression. We have examined the relationship between polymorphisms of the TGF-β1 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-β1 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-β1, 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-β1 -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.

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Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 110-744, Korea
    Yoon Jun Kim

Authors

  1. Yoon Jun Kim
  2. Hyo-Suk Lee
  3. Jong Pil Im
  4. Byung-Hoon Min
  5. Hyun Dae Kim
  6. Ji Bong Jeong
  7. Jung-Hwan Yoon
  8. Chung Yong Kim
  9. Myung Soo Kim
  10. Jun Yeon Kim
  11. Ji Hyun Jung
  12. Lyoung Hyo Kim
  13. Byung Lae Park
  14. Hyoung Doo Shin

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