GSTM1/T1 Genotypes and Benzo(A)Pyrene Hemoglobin Adducts in Maternal and Fetal Blood

Both genetic and environmental factors are involved in the development of cancer. The capacity to metabolize certain drugs and carcinogens is known to be variable in humans and appears to be of critical importance in determining the risk an individual has of developing cancer when exposed to carcinogens. For many phase I and phase II enzyme systems involved in foreign compound metabolism it is now understood that germ-line genetic variation within the genes encoding these enzymes leads to altered phenotypic expression impacting the metabolic capacity of the individual. This genetic variation is referred to as genetic polymorphism and the study of the association between genetic polymorphism and the resulting phenotypic changes in drug or foreign compound metaboism is referred to as pharmacogenetics. This variation in metabolic capacity is linked to environment-gene interactions on carcinogenesis and has been well demonstrated by enzymes that are involved in the metabolism of carcinogens including several human cytochrome P450 enzymes as well as certain glutathione S-transferases and N-acetyltransferases. The genetic lesion may involve a single but critical base pair change or complete gene deletion. Screening assays based on PCR amplification coupled to restriction fragment length polymorphism (RFLP) analysis or allele specific PCR have been developed to correlate genetic polymorphism with phenotypic expression and susceptibility to genotoxicity or carcinogenesis. The phase II enzymes, including GSTs, N-acetyltransferases, as well as epoxide hydrolase, are all involved in the detoxification of activated metabolites of carcinogens, including those carcinogens found in tobacco smoke. The substrates of GSTs include benzo(a)pyrene as well as other carcinogens. In the present study, we investigated the relationship between polymorphism of glutathione S-transferase in maternal and fetal cord blood samples obtained at delivery and correlated genotype with presence of hemoglobin adducts to the tobacco carcinogen benzo(a)pyrene.