Association of environmental benzo[a]pyrene exposure and DNA methylation alterations in hepatocellular carcinoma: A Chinese case-control study
Association of environmental benzo[a]pyrene exposure and DNA methylation alterations in hepatocellular carcinoma: A Chinese case-control study
复制标题
环境苯并[a]芘暴露与肝细胞癌 DNA 甲基化改变的关联：一项中国病例对照研究。
DOI：
10.1016/j.scitotenv.2015.10.003
复制
发表时间：
2016-01-15
影响因子：
9.8
通讯作者：
Shen, Heqing
中科院分区：
文献类型：
--
作者：
Tian, Meiping;Zhao, Benhua;Shen, Heqing
流行病学研究表明，环境危险因素和表观遗传学改变在肝细胞癌的多阶段发展过程中起重要作用。然而，在肝细胞癌的发展过程中，环境因素和肿瘤抑制基因(TSG)的DNA甲基化之间的关联仍然不明确。了解可能的相互作用如何影响风险，可能有助于深入了解肝癌发生的复杂性。本研究采集了厦门市90例肝癌患者和99例健康志愿者(中国)的血样，并记录了选定的环境危险因素[如苯并[a]芘(B[a]P)、乙型或丙型肝炎病毒(乙肝或丙型肝炎病毒)感染、吸烟和饮酒]的数据，确定了病例组中显著高于对照组的因素(P<；0.05)。为了评估表观遗传学改变与肝细胞癌危险因素之间的关系，采用高分辨熔融(HRM)分析对TSGs的血清DNA甲基化进行了定量。我们的结果清楚地表明，与对照组相比，病例组解毒基因[谷胱甘肽-S-转移酶PI]启动子区域的甲基化模式明显升高。此外，GSTP启动子高甲基化和B[a]P二醇环氧化物白蛋白(BPDE-Alb)与肝细胞癌的发生呈正相关。我们的流行病学和体外细胞模型研究表明，GSTP启动子DNA甲基化调节该基因的表达。此外，GSTP还在B[a]P的解毒和对B[a]P诱导的肝细胞毒性和肝癌变的潜在保护作用中发挥重要作用。(C)2015爱思唯尔B.V.保留所有权利。
Epidemiological studies implicate environmental risk factors and epigenetic alterations in the multistage process of hepatocellular carcinoma (HCC) development. However, associations between environmental factors and DNA methylation of tumour suppressor genes (TSGs) in HCC development remain ambiguous. Understanding how possible interactions influence risk may provide insights into the complexity of hepato-carcinogenesis. For this study, blood samples were collected from HCC patients (n = 90) and healthy volunteers (n = 99) from Xiamen (China) and data for selected environmental risk factors [e.g., benzo[a] pyrene (B[a]P), hepatitis B or C virus (HBV or HCV) infection, smoking and alcohol consumption] were recorded; factors identified as significantly higher (P < 0.05) amongst case subjects compared to controls were identified. In order to assess associations for epigenetic alterations and HCC risk factors, serum DNA methylation of TSGs was quantified using high-resolution melting (HRM) analysis. Our results clearly indicate elevated methylation patterns for detoxification gene [glutathione-S-transferase Pi (GSTP)] promoter regions in cases compared to control subjects. Additionally, GSTP promoter hypermethylation and B[a] P diol epoxide-albumin (BPDE-Alb) were positively correlated with HCC incidence. Our epidemiological and in vitro cell model studies indicated that GSTP promoter DNA methylation regulates this gene's expression. Moreover, GSTP also plays an important role in B[a]P detoxification and potential protective role against B[a] P-induced liver cell toxicity and hepato-carcinogenesis. (C) 2015 Elsevier B.V. All rights reserved.