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Diet derived polycyclic aromatic hydrocarbons and its pathogenic roles in colorectal carcinogenesis
Tracie Cheng1, Alfred K Lam1, Vinod Gopalan1
1Cancer Molecular Pathology, School of Medicine & Dentistry, Griffith University, Gold Coast, Queensland 4222, Australia.
Abstract:
Polycyclic aromatic hydrocarbon (PAHs) are molecules that contaminate meat products during the high-temperature cooking of meat. This study reviewed the pathogenic roles of meat derived polycyclic aromatic hydrocarbons in the carcinogenesis of colorectal cancer (CRC). Ingested PAHs undergo xenobiotic metabolism resulting in the activation of genotoxic metabolites that can induce DNA damage in the colorectum. Genetic polymorphisms in PAH xenobiotic enzymes are linked to the risk of CRC and suggest a role for PAH-meat ingestion in carcinogenesis of colorectal malignancies. Furthermore, PAH specific DNA adducts have been identified in colorectal cancer tissue and linked to high meat intake. DNA adduct resolution is mediated by the nucleotide excision repair, and polymorphisms within genes of this repair pathway and high meat intake are associated with increased CRC risk. In the literature, there is evidence from metabolic enzyme gene variants, DNA repair genes, PAH metabolites, and epidemiological studies suggesting PAH involvement in CRC.
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