Biochemical and Molecular Epidemiology of Cancer
摘要
Examples of practical approaches to molecular epidemiology of human cancer are described .Biomarkers of carcinogen exposure or inherited host factors for cancer susceptibility are discussed.Major advances have been made in the detection of carcinogen-macromolecular adducts through the use of high performance liquid chromatography,immunoaffinity chromatography,the ^32P-postlabeling assay,enzyme immunoassays ,gas chromatography/mass spectroscopy and synchronous spectrophotofluorimety.The polycyclic aromatic hydrocarbon-DNA adducts are the most extensively studied in this field and together with antibodies to these adducts found in human serum,they have become useful indicators of exposure to carcinogens.Assays for various kinds of alky1-DNA adducts have also been developed and the presence of these adducts have been documented in human tissues.Carcinogen-protein adducts have proven to be useful molecular dosimeters of carcinogen exposure.For example,4-aminobipheny1 hemoglobin adducts are highly correlated with exposure to tobacco smoke.The study of the molecular aspects of interindividual differences in the metabolism and activation of xenobiotics and other genetic markers[DNA-restriction fragment length polymorphisms(PFLPs),mutations,and functional loss of specific genes in carcinogenesis] is an emerging new field that is discussed in the context of genetic susceptibility to cancer .The cytochrome P450 phenotypes and acetylation phenotype are examples of genetic markers that indicate an individual's potential for metabolism of exogenous substances.Further ,inherited genetic polymorphic markers,e,g,DNA-RFLPs at protooncogene loci(HRAS-1 and L-myc) have been examined in a case-control strdy of lung cancer.Data concerning mutations of protooncogenes(H-,K-,and N-RAS) and tumor suppressor genes(retinoblastoma and p53 genes)in various common cancers are providing evidence of multiple genetic lesions that occur during the multistage process of carcinogenesis.