Effect of cytokine genotypes on the hepatitis B virus-hepatocellular carcinoma association
Effect of cytokine genotypes on the hepatitis B virus-hepatocellular carcinoma association
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作者：
Nieters, A;Yuan, JM;Yu, MC
背景。在中国广西南部，在围产期从携带者母亲那里获得的乙型肝炎病毒（HBV）慢性感染是导致肝细胞癌的主要原因。然而，只有少数乙肝病毒携带者最终发展为肝细胞癌。作者假设细胞因子基因型可能是 HBV 相关肝细胞癌风险的重要共同决定因素。方法。作者检查了 250 名原发性肝细胞癌患者（病例）和 250 名医院对照者中 T 辅助细胞 1 (Th1) 和 Th2 细胞因子基因多态性之间的相关性，这些对照者按年龄、性别、种族、居住地和中国广西南宁市的入院月份与索引病例进行了单独匹配。 结果。相对于假定的高活性基因型，干扰素 γ、白细胞介素 12 (IL12) 和 IL18 的每种低活性基因型与肝细胞癌风险的统计上不显着的增加 (40-60%) 相关。调整潜在混杂因素后，这种风险随着低活性 Th1 基因型数量的增加而增加（趋势的双侧 P 值 = 0.04）。相反，个体 Th2（IL4、IL10）低活性基因型与肝细胞癌风险降低无统计学意义相关。在调整潜在的混杂因素后，这种风险随着低活性 Th2 基因型数量的增加而降低（趋势的双侧 P 值 = 0.01）。具有最大数量（即 3 个）低活性 Th1 基因和最小数量（即 0 个）低活性 Th2 基因的个体显示出 20.0 的相对风险（95% 置信区间，1.7-235.0）。结论。由基因控制的细胞介导的免疫反应减弱似乎是乙型肝炎相关肝细胞癌发生的重要风险决定因素。 (C) 2005 年美国癌症协会。
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 gamma, 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. (C) 2005American Cancer Society.