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Human Molecular Genetics, 2003, Vol. 12, No. 8 901-906
DOI: 10.1093/hmg/ddg104
© 2003 Oxford University Press

Interleukin 10 haplotype associated with increased risk of hepatocellular carcinoma

Hyoung Doo Shin1, Byung Lae Park1, Lyoung Hyo Kim1, Ji Hyun Jung1, Jun Yeon Kim1, Jung Hwan Yoon2, Yoon Jun Kim2 and Hyo-Suk Lee2,*

1Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul 110-834, Korea and 2Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yungun-Dong, Chongro-Gu, Seoul 110-744, Korea

Received January 10, 2003; Accepted February 19, 2003

Interleukin 10 (IL10) is a powerful Th-2 cell cytokine produced by lymphoid cells that exerts its functions by inhibiting macrophage/monocyte and T-cell lymphocyte replication and secretion of inflammatory cytokines (IL1, TNFA, TGFB, IL6, IL8 and IL12). Genetic association analysis of a well-characterized HBV cohort revealed that one of IL10 haplotypes, IL10-ht2, was strongly associated with hepatocellular carcinoma (HCC) occurrence in gene dose-dependent manner. The frequency of susceptible IL10-ht2 was much higher in HCC patients and significantly increased in order of susceptibility to HBV progression from chronic hepatitis to liver cirrhosis and HCC among hepatitis B patients. In addition, survival analysis clearly showed that the onset age of HCC was also accelerated among chronic hepatitis B patients who were carrying IL10-ht2. Increased IL10 production mediated by IL10-ht2 suggests that up-regulated IL10 accelerates progression of chronic HBV infection, especially to HCC development.

* To whom correspondence should be addressed at: Department of Internal Medicine, Seoul National University Hospital, 28 Yungun-Dong, Chongro-Gu, Seoul 110-744, Korea. Tel: +82 27457557; Fax: +82 27448243; Email: hsleemd{at}snu.ac.kr


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