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

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Abstract
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.