Genetic Polymorphisms of Smoking-related Carcinogen Detoxifying Enzymes and Head and Neck Cancer Susceptibility

Smoking and the consumption of alcohol are the main risk factors for head and neck cancer. However, inter-individual variation in the activity of enzymes involved in the detoxification of tobacco smoke (pro)carcinogens, such as microsomal epoxide hydrolase (mEH), glutathione-S-transferases (GSTs) and uridine 5′-diphosphate (UDP)-glucuronosyltransferase (UGTs), may influence the process of carcinogenesis. Genetic polymorphisms of these enzymes may alter their activity and may thus modulate the risk for squamous cell carcinomas of the head and neck (SCCHN). A literature review on the role of mEH, GSTs and UGTs polymorphisms in relation to SCCHN was performed and the results summarized. For mEH polymorphisms, some of the studies revealed a relationship between genetic polymorphisms of these enzymes and an altered risk for SCCHN, whereas others did not. The presence of null polymorphisms in GSTM1 or GSTT1 were associated with an increased risk for SCCHN. For the UGTs, only variants in UGT1A7 and UGT1A10 have been studied, both of which were associated with an altered risk for SCCHN.