Association of transforming growth factor-b1 gene polymorphisms with a hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection.
- Author:
Yoon Jun KIM
1
;
Hyo Suk LEE
;
Jong Pil IM
;
Byung Hoon MIN
;
Hyun Dae KIM
;
Ji Bong JEONG
;
Jung Hwan YOON
;
Chung Yong KIM
;
Myung Soo KIM
;
Jun Yeon KIM
;
Ji Hyun JUNG
;
Lyoung Hyo KIM
;
Byung Lae PARK
;
Hyoung Doo SHIN
Author Information
1. Department of Internal Medicine, Seoul National University College of Medicine Seoul 110-744, Korea. hsleemd@snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
chronic hepatitis;
HBV;
genetic susceptibility;
hepatocellular carcinima;
single nucleotide polymorphism;
transforming growth factor-beta1
- MeSH:
Adult;
Aged;
Carcinoma, Hepatocellular/etiology/*genetics;
Female;
Hepatitis B/complications/*genetics;
Human;
Liver Neoplasms/etiology/*genetics;
Male;
Middle Aged;
Polymorphism, Single Nucleotide/*genetics;
Risk Factors;
Transforming Growth Factor beta/*genetics;
Variation (Genetics)
- From:Experimental & Molecular Medicine
2003;35(3):196-202
- CountryRepublic of Korea
- Language:English
-
Abstract:
Transforming growth factor-b1 (TGF-beta 1) can act as both a tumor suppressor and a stimulator of tumor progression. We have examined the relationship between polymorphisms of the TGF-beta 1 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-beta 1 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-beta 1, 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-beta 1 -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.
