Association of environmental benzo[a]pyrene exposure and DNA methylation alterations in hepatocellular carcinoma: A Chinese case–control study

• Published in: The Science of the total environment Vol. 541; pp. 1243 - 1252
• Main Authors: Tian, Meiping, Zhao, Benhua, Zhang, Jie, Martin, Francis L., Huang, Qingyu, Liu, Liangpo, Shen, Heqing
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.01.2016
• Subjects: Adult; alcohol drinking; Alterations; B[a]P; benzo(a)pyrene; Benzo(a)pyrene - toxicity; blood sampling; blood serum; Carcinoma, Hepatocellular - epidemiology; Carcinoma, Hepatocellular - metabolism; Case control study; Case-Control Studies; China; China - epidemiology; correlation; cytotoxicity; Deoxyribonucleic acid; DNA Methylation; Ecological risk assessment; Environmental Exposure - statistics & numerical data; environmental factors; Environmental Pollutants - toxicity; Epidemiology; Epigenetic; epigenetics; Female; Genes; glutathione transferase; GSTP; hepatitis B; Hepatitis B virus; Hepatitis C virus; Hepatocellular carcinoma; hepatocytes; hepatoma; Humans; Liver Neoplasms - epidemiology; Liver Neoplasms - metabolism; Male; Mathematical models; melting; Methylation; Middle Aged; patients; promoter regions; protective effect; Risk analysis; risk factors; tumor suppressor genes; viruses; volunteers; China; China, People's Rep; DNA methylation; GSTP; Hepatocellular carcinoma; Case control study; Epigenetic; B[a]P
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2015.10.003

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. [Display omitted] •Environmental BaP exposure in hepatocellular carcinoma is higher than control.•GSTP gene promoter DNA hypermethylation is frequent in hepatocellular carcinoma.•GSTP gene promoter DNA hypermethylation results in GSTP mRNA expression silence.•GSTP mRNA expression plays important roles against BaP-induced liver cell toxicity.•BaP exposure enhances GSTP methylated subject susceptibility of hepatocarcinogenesis.