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

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.

Combined Effects of Six Cytokine Gene Polymorphisms and SNP-SNP Interactions on Hepatocellular Carcinoma Risk in Southern Guangxi, China

“…In this study, we found that individuals with four to six risk genotypes (i.e., IL-2-330AA, IFN-γ-1615AG/ AA, IL-1β-511CT/TT, IL-1β-1464CG/GG, IL-6-572GG/ CG, and IL-10-592TG/GG) may have an increased HCC risk. Consistent with the result of Nieters et al (2005), the present study found that the synergistic rather than the individual effects of cytokine gene SNPs were associated with an increased HCC risk.…”

Genetic polymorphisms in the methylenetetrahydrofolate reductase and thymidylate synthase genes and risk of hepatocellular carcinoma

“…The designs of the 2 studies have been described previously. 8,29 Permission to conduct this study had been obtained from the Institutional Review Boards at the University of Southern California and the Guangxi Cancer Institute. Separate informed consent forms for interview and biospecimen collection were obtained from each study participant.…”

“…The assays used for testing serologic markers of HBV and HCV infections have been described previously. 8, 29 Briefly, we tested all study samples for the presence of hepatitis B surface antigen in serum using commercialized kits (AUSRIA, Abbott Laboratories, North Chicago, IL), and negative samples (for the Los Angeles study only) were further tested for the presence of antibodies to the hepatitis B core antigen using standard testing kits (Corab, Abbott Laboratories, North Chicago, IL). All samples were tested for the presence of antibodies to the hepatitis C virus (anti-HCV) in serum using the enzyme linked immunosorbent assay version 2.0 kit manufactured by Ortho Diagnostic Systems, with confirmation of positive samples using RIBA version 2.0 (Chiron, Emeryville, CA).…”

Development of a Listeria monocytogenes-based vaccine against hepatocellular carcinoma

“…Thus, when carrying fusion peptides, Lmdd is able to elicit a T-cell response against various epitopes simultaneously. In HCC patients, it has been demonstrated that a deviation to a Th2 immune response occurs (Nieters et al, 2005). In our Tg animals, vaccination with Lmdd-MPFG led to a shift in the Th1/Th2 balance toward a Th1 dominant immune response, as demonstrated by the increased secretion of the Th1 cytokine IFN-g in the stimulated splenocytes by ELISA and ELISPOT assays.…”