Segregation analysis of hepatocellular carcinoma in a moderately high-incidence area of East China.
Segregation analysis of hepatocellular carcinoma in a moderately high-incidence area of East China.
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DOI：
10.3748/wjg.v9.i11.2428
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发表时间：
2003-11
影响因子：
4.3
通讯作者：
Ru-lin Cai;W. Meng;Hong-yan Lu;Wen-yao Lin;F. Jiang;F. Shen
中科院分区：
文献类型：
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作者：
Ru-lin Cai;W. Meng;Hong-yan Lu;Wen-yao Lin;F. Jiang;F. Shen
目的探讨中国东部中高发区肝细胞癌的遗传方式。方法对江苏省海门市210个肝癌先证者确定的210个家系(3315人)进行家系调查。用SEGRANB软件进行简单分离分析。估计确诊概率(Pi)、分离比(P)和散发性病例比例(X)。应用S.A.G.E.的REGTL程序进行复杂分离分析，对3212名个体的数据进行模型拟合，在REGTL程序中考虑了个体的乙肝表面抗原状态和不同的发病年龄。结果SEGRANB法估计的分离比为0.191。确诊概率为0.0266，散发性病例比例为0.465。复合分离分析结果表明，影响肝癌发病年龄分布的主效基因为孟德尔常染色体隐性遗传，与数据拟合最好。在最佳拟合的隐性模型中，疾病等位基因频率为0.11138。HBs Ag阳性将显著增加发生肝细胞癌的风险。结论提示至少有一个主效基因参与了肝癌发病年龄偏早的遗传易感性。血清HBs Ag阳性状态可显著增加发生肝癌的风险，这为遗传和环境危险因素之间的相互作用提供了强有力的支持。
AIM To explore the mode of inheritance of hepatocellular carcinoma (HCC) in a moderately high-incidence area of East China. METHODS A pedigree survey was conducted in 210 families (3315 individuals) ascertained through 210 HCC probands in Haimen, Jiangsu Province. Simple segregation analysis was conducted using SEGRANB software. The probability of ascertainment (pi), segregation ratio (p), and the proportion of sporadic cases (x) were estimated. Complex segregation analysis was performed using the REGTL program of S.A.G.E. Models were fitted on the data of 3212 individuals that allowed for personal HBsAg status and variable age of onset in REGTL program. RESULTS The estimate of segregation ratio was 0.191 by SEGRANB. The probability of ascertainment was 0.0266, and the proportion of sporadic cases was 0.465. The results of complex segregation analysis showed that Mendelian autosomal recessive inheritance of a major gene that influenced the age of onset distribution of HCC, provided the best fit to the data. In the best-fitting recessive model, the frequency of the disease allele was 0.11138. HBsAg seropositive status would significantly increase the risk of developing HCC. CONCLUSION These results suggest that at least one major gene is involved in the genetic predisposition to develop HCC at an earlier age of onset. The seropositive HBsAg status can significantly increase the risk of developing HCC, which provides strong support for the interaction between genetic and environmental risk factors.