摘要目的 探讨肝细胞癌(UCC)组织中Ras相关结构域家族1A( RASSF1A)基因甲基化与环境因素的关系.方法 采用甲基化特异性聚合酶链反应检测80例HCC组织中RASSF1A基因甲基化状态,免疫组织化学法检测HCC组织中黄曲霉素B1( AFB1 )-DNA加合物和多环芳烃(PAHs) -DNA加合物的水平,并结合临床资料进行统计分析.结果 RASSF1A基因甲基化率在肝癌组织中(60/80)显著高于癌旁组织(33/80,P＜0.01).HCC组织中RASSF1A基因甲基化率在AFB1-DNA加合物阳性组(43/51)高于AFB1-DNA加合物阴性组(17/29,P＜0.05)；在PAHs-DNA加合物阳性组(39/45)高于PAH-DNA加合物阴性组(21/35,P＜ 0.05).结论 HCC组织中RASSF1A基因甲基化与环境致癌因素AFBI -DNA加合物、PAHs-DNA加合物水平密切相关.

abstractsObjective To investigate the relationship between ras association domain family 1A gene (RASSF1 A) methylation and environmental factors to the hepatocellular carcinoma (HCC).Methods The methylation of RASSF1A was determined by methylation specific polymerase chain reaction (PCR) in 80 genomic DNAs from patients with HCC.Aflatoxin B1 (AFB1)-DNA adducts and polycyclic aromatic hydrocarbons (PAHs)-DNA adducts in tumor tissues were determined by immunohistochemistry.The association between RASSFI A methylation and environmental factors taking into consideration of the clinical biological material was statistically analyzed.Results RASSF1A promoter hypermethylation was detected in 60 of the 80 HCC tissues (75.0％).Of the paired corresponding adjacent tissues from the 80 HCC patients,aberrant methylation was detected in 33 (41.3％).The positive rate for RASSF1A methylation was significantly higher in the HCC tissues than in the paired controls (P ＜O.O1 ).For AFBI-DNA adducts,the positive rate by methylation specific polymerease chain reaction (MSP) was significantly higher in positive cases (43/51,84.3％ ) than in negative cases (17/29,58.6％,P＜0.01 ).For PAHs-DNA adduct,the positive rate by MSP was also significantly higher in positive cases ( 39/45,86.7％ ) than in negative cses ( 21/35,60.0％,P ＜ O.05 ).Conclusion Statistically significant correlations were observed between RASSF1A methylation and AFB1-DNA adducts or PAHs-DNA adducts in the HCC tissues.