Association of transforming growth factor-beta1 gene polymorphisms with a hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection.
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.
Kim
Yoon Jun
YJ
Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Korea.
Lee
Hyo-Suk
HS
Im
Jong Pil
JP
Min
Byung-Hoon
BH
Kim
Hyun-Dae
HD
Jeong
Ji Bong
JB
Yoon
Jung-Hwan
JH
Kim
Chung Yong
CY
Kim
Myung Soo
MS
Kim
Jun Yeon
JY
Jung
Ji Hyun
JH
Kim
Lyoung Hyo
LH
Park
Byung Lae
BL
Shin
Hyoung Doo
HD
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
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1