RASSF1A Hypermethylation is Associated with Aflatioxin B1 and Polycyclic Aromatic Hydrocarbon Exposure in Hepatocellular Carcinoma

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.