Relationship Of DNA Damage And Genetic Polymorphisms In DNA Repair Genes To Risk Of Esophageal Squamous Cell Carcinoma

Recent improvements in the ability to detect chemically modified bases in DNA have revealed that the genetic material incurs damage not only by foreign mutagens/carcinogens, but also by reactive products of normal physiological processes with endogenous origin. Malondialdehyde is a naturally occurring product of lipid peroxidation and prostaglandin biosynthesis that is mutagenic and carcinogenic. It reacts with DNA to form adducts to deoxyguanosine and deoxyadenosine. The major adduct to DNA is a pyrimidopurinone called M₁-dG, which is mutagenic in bacteria with site-specific mutagenesis experiments.The endogenous formation of malondialdehyde and its genotoxicity and mutagenicity suggest that M₁-dG may contribute significantly to cancer development linked to lifestyle and dietary factors. Low intake or low plasma levels of micronutrients that have antioxidative activity have been associated with increased risk of esophageal cancer. Poor cellular antioxidant status promotes oxidative DNA damage induced by oxidants generated by physiological metabolism or by other oxidative stress such as that resulted from lifestyle and dietary factors, which, in turn, may contribute to carcinogenesis of the esophagus. However, little is known about the oxidative DNA damage in both normal and cancerous esophageal tissues.