Correlation analysis of ras association domain family 1A gene methylation and environmental factors to hepatocellular carcinoma

Abstract

Objective To investigate the relationship between ras association domain family 1A gene (RASSF1 A) methylation and environmental factors to the hepatocellular carcinoma (HCC).Methods The methylation of RASSF1A was determined by methylation specific polymerase chain reaction (PCR) in 80 genomic DNAs from patients with HCC.Aflatoxin B1 (AFB1)-DNA adducts and polycyclic aromatic hydrocarbons (PAHs)-DNA adducts in tumor tissues were determined by immunohistochemistry.The association between RASSFI A methylation and environmental factors taking into consideration of the clinical biological material was statistically analyzed.Results RASSF1A promoter hypermethylation was detected in 60 of the 80 HCC tissues (75.0％).Of the paired corresponding adjacent tissues from the 80 HCC patients,aberrant methylation was detected in 33 (41.3％).The positive rate for RASSF1A methylation was significantly higher in the HCC tissues than in the paired controls (P ＜O.O1 ).For AFBI-DNA adducts,the positive rate by methylation specific polymerease chain reaction (MSP) was significantly higher in positive cases (43/51,84.3％ ) than in negative cases (17/29,58.6％,P＜0.01 ).For PAHs-DNA adduct,the positive rate by MSP was also significantly higher in positive cases ( 39/45,86.7％ ) than in negative cses ( 21/35,60.0％,P ＜ O.05 ).Conclusion Statistically significant correlations were observed between RASSF1A methylation and AFB1-DNA adducts or PAHs-DNA adducts in the HCC tissues. Key words: Hepatocarcinogenesis; Aflatoxin B; Ras association domain family 1A gene; Methylation