HLA-DRB Type, Hepatitis B Viral Factors, and Hepatocellular Carcinoma Risk: Independent and Interactive Effects

• Main Authors: CHENG, YU-CHING, 鄭郁青
• Other Authors: YU, MING-WHEI
• Format: Others
• Language: en_US
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/87318078788426531365

碩士 === 國立臺灣大學 === 流行病學研究所 === 91 === Background: Hepatitis B virus (HBV) is the most important risk factor for hepatocellular carcinoma (HCC) in Taiwan. However, host genetic factors may be involved in hepatocarcinogenesis, given the evidence that only a small fraction of HBV carriers will eventually develop HCC, and there is a strong familial aggregation of HCC. Human leukocyte antigen (HLA) plays an important role in the inflammatory response induced by HBV. The aims of this study were to evaluate the independent effect of HLA-DRB genes and its interactive effects with HBV genotypes and DNA titer on the transition from healthy HBV carrier state to HCC. Methods: A case-control study nested in a cohort of 4,841 male HBV carriers was conducted. Blood samples drawn at baseline were used for HLA-DRB/HBV genotyping and HBV DNA titer analysis. For each HCC case, two controls were randomly selected from the cohort and were matched to cases by year of birth and the time of blood drawn. We determined HLA-DRB1, 3, 4, 5 alleles in 105 HCC cases and 175 controls with a two-step high-resolution HLA-DRB genotyping method. HBV genotypes and DNA titer were analyzed for 99 cases and 171 controls with available serum samples. The HBV DNA titer was undetectable for 4 cases and 18 controls, and the HBV genotypes could not be classified for 6 cases and 19 controls. Results: While certain DRB1 alleles, such as DRB1*0405, *1401, and *16021 appeared to be decreased among cases relative to controls, DRB1*08032, 12011, and 15011 appeared to be increased among cases relative to controls. The multivariate-adjusted ORs for the presence of the former three alleles were 0.29 (95%CI=0.10 to 0.82), 0.19 (95%CI=0.05 to 0.69) and 0.66 (95%CI=0.23 to 1.87), respectively. The multivariate-adjusted ORs for the presence of the latter three alleles were of 1.78 (95%CI=0.76 to 4.20), 2.53 (95%CI=0.95 to 6.78), and 1.95 (95%CI=0.80 to 4.78), respectively. After adjusting multiple comparisons, HLA-DRB loci alone was not statistically significantly associated with risk of HCC. Infection with HBV genotype C or having a HBV DNA titer larger than 113,100 copies/mL was at increased risk for HCC (multivariate adjusted OR=4.50 [95%CI=2.39 to 8.48] and 4.63 [95%CI=1.95 to 11.02], respectively). HLA-DRB1 genotype strongly interacted with HBV genotypes and DNA titer in HCC. Compared with HBV carriers without a high-risk HLA-DRB1 allele who had HBV non-C genotype and lower HBV DNA titer, the OR of HCC was as high as 42.27 for those harboring a high-risk HLA-DRB1 allele who had HBV C genotype and a HBV DNA level higher than the lowest value of the upper tertile of DNA titer in controls. Conclusions: HLA-DRB genes may interact with HBV genotypes and DNA titer in the transition from HBV carrier state to HCC.