title: RASSF1A hypermethylation is associated with aflatoxin B1 and polycyclic aromatic hydrocarbon exposure in hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Minimally Invasive Surgery, The Affiliated Hospital of Nantong University, Jiangsu, , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.forename: Wan-Jiang
authors.initials: WJ
authors.lastname: Xue
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Sha
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Rui
authors.forename: Hou-Xiang
authors.initials: HX
authors.lastname: Li
authors.forename: Qin-Sheng
authors.initials: QS
authors.lastname: Mao
mesh_terms: D016604:Aflatoxin B1 / Q000009:adverse effects* / Q000378:metabolism; D002274:Carcinogens, Environmental / Q000009:adverse effects* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D016009:Chi-Square Distribution; D002681:China; D018736:DNA Adducts / Q000378:metabolism; D019175:DNA Methylation; D004781:Environmental Exposure; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects* / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002274:Carcinogens, Environmental; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; C411762:RASSF1 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D016604:Aflatoxin B1