Polymorphisms of drug-metabolizing enzymes in healthy nonagenarians and centenarians: Difference at GSTT1 locus

Drug metabolizing enzymes are involved in the detoxification of several dru gs, environmental substances, and carcinogenic compounds, and their polymor phisms have been associated with risk for a variety of cancer. In this pape r, we compared the frequency of polymorphisms in cytochrome P450-1A1 gene ( CYP1A1), a phase 1 gene (oxidation, activation), and of two polymorphisms o f glutathione S-transferase enzymes (GSTM1, GSTT1), two phase 2 genes (conj ugation, detoxification). Two groups were studied and compared, i.e., 94 no nagenarians and centenarians and 418 control subjects of younger age. A sig nificant difference in the proportion of nonagenarians and centenarians hom ozygotes for a GSTT1 deletion (28%) was observed in comparison to control s ubjects (19%, P = 0.03). The distribution of the other gene polymorphisms d id not differ in the two groups. These findings on phase 2 drug-metabolizin g enzyme gene polymorphisms may help in disentangling gene-environmental in teractions which can have a role in successful aging and longevity, as well as in cancer incidence in the oldest old. (C) 2001 Academic Press.