Fig. 1

Metabolism of chemotherapeutic drugs-related gene polymorphisms. In cancer cells 5-FU is converted to 5-fluorodeoxyuridine monophosphate (5-FdUMP). 5-FdUMP inhibits the DNA synthesis by competing with deoxyuridine monophosphate (dUMP) for binding to thymidylate synthase (TS) in a complex that is stabilized by the reduced folate 5,10-methylene tetrahydrofolate. 5-FU can also inhibit RNA synthesis in a pathway that involves its metabolism to 5-fluorouridinemonophosphate (5-FUMP) and subsequent conversion to 5-fluorouridine triphosphate (5-FUTP) via 5-fluorouridine diphosphate (5-FUDP). The main effect of cyclophosphamide is due to its metabolite phosphoramide mustard that forms DNA crosslinks both between and within DNA strands at guanine N-7 positions (known as interstrand and intrastrand crosslinkages, respectively). This is irreversible and leads to cell apoptosis. Anthracyclines inhibit DNA and RNA synthesis by intercalating between base pairs of the DNA/RNA strand, thus preventing the replication of rapidly growing cancer cells. In addition, they can generate reactive oxygen species (ROS) damaging DNA, proteins and cell membranes. Glutathione S-transferases (GSTs) catalyse the detoxification of alkylating agents used in chemotherapy and/or ROS