原发性肝癌的遗传流行病学研究

A study on the genetic epidemiology of hepatocellular carcinoma

目的 研究原发性肝癌的遗传模式 ,探讨本病的遗传与环境的交互作用。方法 采用Penrose法、简单分离分析和Falconer法对乙型肝炎表面抗原 (HBsAg)阳性队列中的 10 0例原发性肝癌家系资料进行遗传流行病学研究。先证者样本来自同地区 9万名 8年随访队列人群 ,分析遗传模式并将队列中家系样本发病情况分别与队列人群和一般人群的发病情况进行比较 ,计算遗传度。结果 先证者家系一级亲属肝癌发生率为 4 .0 % ,高于一般人群发生率 (0 .4 4 % ) ,也高于队列人群的肝癌发生率 (1.0 3% )。HBsAg阳性在先证者家系中存在聚集 ,且HBsAg阳性与肝癌的发生有强相关(OR =8.4 4 ,95 %CI :3.37～ 2 0 .0 6 ,P <0 .0 0 1) ;应用Penrose法计算 ,同胞肝癌发生率 一般人群肝癌发生率 (s q)接近 1 q1 2 ;简单分离分析提示不符合单因子遗传模式 ;与一般人群遗传度相比 (5 9%±7% ) ,队列人群遗传度h2 =4 2 %± 6 % ,P <0 .0 5。在控制了HBsAg后 ,一般人群遗传度下降为4 7%± 7% ,队列人群遗传度下降为 2 9%± 8%。结论 肝癌不符合单基因遗传模式 ,为一多因子疾病 ,受遗传与环境的综合影响。

Objective To explore the interaction between inheritance and environment with the aid of research on the genetic modes of hepatocellular carcinoma(HCC). Methods A genetic epidemiological study of HCC was conducted based on the methods of Penrose, simple segregation and Falconer for 100 proband pedigrees from HBsAg positive cohort. The proband samples came from a cohort of 90 000 people who were followed for 8 years. Analyses on genetic modes were carried out and heritability was calculated through the comparision of the proband pedigrees incidence frequence with incidence frequences of the cohort and general population. Results The incidence frequence of first degree relatives was 4.0 %, higher than what was seen in the general population incidence frequence ( 0.44 %) and the cohort ( 1.03 %). A familial aggregation of HBsAg carriers and a strong positive correlation between HBsAg carrier status and HCC were noticed ( OR = 8.44 ,95% CI : 3.37 20.06 , P < 0.001 ). A ratio of the incidence frequence among siblings to the incident frequence among general population ( s/q ) approached 1/ q 1/2 by Penrose method, but simple segregation did not show agreement with single gene inheritance. The heritability from positive cohort was 42%± 6% ( P < 0.05 ), compared with the heritability ( 59%± 7%) of general population. When the effect of the HBsAg was under control, the heritability from positive cohort turned to be 29%± 8% ( P < 0.05 ), compared with the heritability ( 47%± 7%) of general population. Conclusion Our findings suggested that HCC followed a multifactorial mode rather than single inheritance. An interaction effect of inheritance and environment on HCC was also noticed.