Effect of cytokine genotypes on the hepatitis B virus‐hepatocellular carcinoma association

• Published in: Cancer Vol. 103; no. 4; pp. 740 - 748
• Main Authors: Nieters, Alexandra, Yuan, Jian‐Min, Sun, Can‐Lan, Zhang, Zhen‐Quan, Stoehlmacher, Jan, Govindarajan, Sugantha, Yu, Mimi C.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.02.2005; Wiley-Liss
• Subjects: Adult; Animals; Biological and medical sciences; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - virology; Chinese; cytokines; Cytokines - genetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; hepatitis B virus; Hepatitis B virus - immunology; Hepatitis B, Chronic - immunology; hepatocellular carcinoma; Humans; interleukins; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Risk Factors; Th1 Cells - physiology; Th2 Cells - physiology; Tumors; Asia; China; Interleukin; Cytokine; Orthohepadnavirus; Hepatic disease; Hepatocellular carcinoma; Genotype; Malignant tumor; interleukins; Virus; Cancerology; Hepadnaviridae; Digestive diseases; Chinese; cytokines; Hepatitis B virus
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.20842

BACKGROUND In Southern Guangxi, China, chronic infection with the hepatitis B virus (HBV) acquired during the perinatal period from carrier mothers is a primary cause of hepatocellular carcinoma. However, only a minority of HBV carriers eventually develop hepatocellular carcinoma. The authors hypothesized that cytokine genotypes may be important codeterminants of the risk of HBV‐related hepatocellular carcinoma. METHODS The authors examined the correlation between polymorphisms in T‐helper 1 (Th1) and Th2 cytokine genes among a group of 250 patients with incident hepatocellular carcinoma (cases) and a group of 250 hospital controls who were matched individually to the index case by age, gender, ethnicity, residence, and month of hospital admission in the city of Nanning, Guangxi, China. RESULTS Relative to the putative high‐activity genotypes, each individual low‐activity genotype of interferon γ, interleukin 12 (IL12), and IL18 was associated with a statistically nonsignificant increase (40–60%) in the risk of hepatocellular carcinoma. This risk increased with increasing numbers of low‐activity Th1 genotypes after adjusting for potential confounders (2‐sided P value for trend = 0.04). Conversely, individual Th2 (IL4, IL10) low‐activity genotypes were associated with a statistically nonsignificant reduced risk of hepatocellular carcinoma. This risk decreased with increasing number of low‐activity Th2 genotypes after adjusting for potential confounders (2‐sided P value for trend = 0.01). Individuals who had the maximum number (i.e., 3) of low‐activity Th1 genes and the minimum number (i.e., 0) of low‐activity Th2 genes showed a relative risk of 20.0 (95% confidence interval, 1.7–235.0). CONCLUSIONS Diminished cell‐mediated immune response, which is controlled genetically, appeared to be an important risk determinant of HBV‐related hepatocellular carcinogenesis. Cancer 2005. © 2005 American Cancer Society. A hospital‐based case–control study of hepatocellular carcinoma conducted in a hyperendemic region, where most cases could be attributed to chronic hepatitis B infection, was used to examine whether genotypes of cytokines known to play a role in hepatitis B infection would influence the risk of hepatocellular carcinoma. The results suggested that genotypes of interferon γ, interleukin 12 (IL12), IL18, IL4, and IL10 may be important codeterminants of the risk for hepatitis B‐related hepatocellular carcinoma. See also pages 654–6.