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

Abstract

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.

Global DNA methylation in a population with aflatoxin B1exposure

“…[21][22][23][24] The association of RASSF1A methylation and AFB 1 -DNA adducts was also reported in another study. 47 These data also suggest that exposure to dietary AFB 1 may alter methylation status of key genes involved in development of HCC. Second, studies have shown that global DNA methylation differs by blood cell type.…”

Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

“…Further, the methylation status of the promoter regions of all three of these genes was significantly positively associated with the level of AFB1-DNA adducts in the tumor tissues, and methylation of MGMT was associated with mutations in the tumor suppressor TP53 gene. Feng, et al also showed that hypermethylation of the RASSF1 gene was associated with AFB1-DNA adducts in human HCC tumor tissue [90]. A significant association was observed between promoter hypermethylation of the glutathione S-transferase pi ( GSTP1 ) gene and the level of AFB1-DNA adducts in human HCC tumor tissue, and a marginally significant association was found for adjacent non-tumor tissue [91].…”

Application of Artificial Neural Networks to Link Genetic and Environmental Factors to DNA Methylation in Colorectal Cancer

“…For example, RASSF1A hypermethylation was linked to the consumption of well-cooked meat, a way of cooking the meat which is known to generate DNA damaging agents ( Figure 5). A previous study has shown that RASSF1A hypermethylation is linked to DNA damaging agents such as aflatoxin B1 and polycyclic aromatic hydrocarbon exposure [50]. Those data, coupled with evidence that RASSF1A functions as a proapoptotic protein and might be involved in later stages of cancer [14,50], indicate that further investigation is warranted concerning environmental factors contributing to the silencing of this gene.…”

“…A previous study has shown that RASSF1A hypermethylation is linked to DNA damaging agents such as aflatoxin B1 and polycyclic aromatic hydrocarbon exposure [50]. Those data, coupled with evidence that RASSF1A functions as a proapoptotic protein and might be involved in later stages of cancer [14,50], indicate that further investigation is warranted concerning environmental factors contributing to the silencing of this gene. Indeed, the underlying mechanisms linking meat consumption to CRC risk are still unclear and there is a need for further studies on differences between white and red meat, between processed and whole red meat and between different types of processed meats, as potential health risks may not be the same for all products [51].…”