Interleukin 10 haplotype associated with increased risk of hepatocellular carcinoma

• Published in: Human molecular genetics 2003-04, Vol.12 (8), p.901-906
• Main Authors: Shin, Hyoung Doo, Park, Byung Lae, Kim, Lyoung Hyo, Jung, Ji Hyun, Kim, Jun Yeon, Yoon, Jung Hwan, Kim, Yoon Jun, Lee, Hyo-Suk
• Format: Article
• Language: English
• Subjects: Age of Onset; Biological and medical sciences; Carcinoma, Hepatocellular - genetics; Gastroenterology. Liver. Pancreas. Abdomen; Haplotypes; Hepatitis B, Chronic - genetics; Humans; Interleukin-10 - genetics; Liver Neoplasms - genetics; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Polymorphism, Single Nucleotide; Risk; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survival Analysis; Tumors
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/ddg104

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.