RASSF1A Hypermethylation is Associated with Aflatioxin B1 and Polycyclic Aromatic Hydrocarbon Exposure in Hepatocellular Carcinoma
RASSF1A Hypermethylation is Associated with Aflatioxin B1 and Polycyclic Aromatic Hydrocarbon Exposure in Hepatocellular Carcinoma
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RASSF1A 高甲基化与肝细胞癌中黄曲霉毒素 B1 和多环芳烃暴露相关
DOI：
10.5754/hge11731
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发表时间：
2012-09-01
影响因子：
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通讯作者：
Mao, Qin-Sheng
中科院分区：
文献类型：
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作者：
Feng, Ying;Xue, Wan-Jiang;Mao, Qin-Sheng
背景/目的：在肝细胞癌（HCC）中经常观察到RASSF 1A高甲基化。但这种表观遗传学改变可能的相关危险因素和预后评估仍不清楚。方法学：检测了103例肝癌组织中RASSF 1A、黄曲霉毒素B1（AFB 1）和多环芳烃（PAH）-DNA加合物的甲基化状态、mRNA和蛋白表达。结果如下：RASSF 1A mRNA（20/103，r=-0.665）和蛋白（21/103，r=-0.761）的表达与RASSF 1A甲基化（82/103）呈负相关。多因素分析表明RASSF 1A甲基化与AFB 1-（p=0.046）和PAH-DNA加合物（p=0.040）相关。其他因素如吸烟、饮酒、B型肝炎病毒感染和临床病理参数与RASSF 1A甲基化无显著相关性。在有和没有RASSF 1A高甲基化的患者之间没有观察到总生存率的差异（p=0.267）。结论：AFB 1和PAH-DNA加合物可能与RASSF 1A甲基化有关。RASSF 1A甲基化状态可能不是肝癌总生存期的适当预测因素。
Background/Aims: RASSF1A hypermethylation is frequently observed in hepatocellular carcinomas (HCC). But the possible related risk factors and prognosis evaluation for this epigenetic alteration are still unknown. Methodology: Methylation status, mRNA and protein expression of RASSF1A, aflatoxin B1 (AFB1) and polycyclic aromatic hydrocarbon (PAH)-DNA adducts, were examined in 103 cases of HCC. Results: The expression of RASSF1A mRNA (20/103, r=-0.665) and protein (21/103, r=-0.761) were negatively related to RASSF1A hypermethylation (82/103). Multivariate analysis indicated that RASSF1A hypermethylation was related to AFB1- (p=0.046) and PAH-DNA adducts (p=0.040). Other factors including smoking, alcohol drinking, hepatitis B virus infection and clinicopathological parameters were not significantly associated with RASSF1A methylation. No difference in overall survival was observed between patients with and without RASSF1A hypermethylation (p=0.267). Conclusions: AFB1- and PAH-DNA adducts may be associated with RASSF1A hypermethylation in hepatocarcinogenesis. RASSF1A methylation status may not be a proper predictor of overall survival for HCC.