Biochemical and molecular epidemiology of human cancer: indicators of carcinogen exposure DNA damage and genetic predisposition.

摘要

The primary goal of biochemical and molecular epidemiology is to identify individuals at high cancer risk by obtaining evidence of high exposure to carcinogens, leading to pathobiological lesions in target cells, and/or increased oncogenic susceptibility due to either inherited or acquired host factors. This emerging and multidisciplinary area of cancer research combines epidemiological and laboratory approaches. Because DNA is considered to be an important target for modification by mutagens and carcinogens, damage to DNA can be used as an internal, molecular dosimeter of carcinogen exposure. The reactive species of these carcinogens may directly bind to DNA to form adducts and may indirectly cause secondary DNA lesions, e.g., via induction of free radicals and aldehydes. Highly sensitive and specific methods have been developed to measure the minute amounts of DNA lesions and DNA repair products found in biological specimens from humans exposed to carcinogens. For example, DNA adducts have been measured in cells and tissues from people occupationally exposed to carcinogenic polycyclic aromatic hydrocarbons. Antibodies recognizing carcinogen-DNA adducts have also been detected in human sera. Inherited predisposition to cancer has been revealed by recent advances in molecular genetics, including restriction-fragment-length polymorphism. For example, the hypothesis that rare alleles of the Ha-ras proto-oncogene are associated with an increased risk of lung cancer is currently being tested. These approaches afford the potential of biochemical and molecular epidemiology to predict disease risk for individual persons, instead of for populations, and before the onset of clinically evident disease.