An investigation into the association between cytochrome P450 and glutathione S-transferase detoxification enzyme polymorphisms and human oral squamous cell carcinoma

Oral squamous cell carcinoma is the sixth commonest cancer in the world. Most patients who develop oral cancer are elderly males who are heavy users of tobacco and alcohol although the incidence is increasing in younger individuals and in those who neither smoke nor drink. Approximately 80% of human cancers result from exposure to xenobiotics. Over the millennia Man has evolved complex families of detoxification enzymes to metabolise and eliminate these harmful compounds. Many of the genes that code for these enzymes are polymorphic, sometimes encoding enzymes with abnormal activity profiles. Numerous diseases have been shown to be more frequent in individuals with abnormal detoxification enzyme activity. This study investigated the association between polymorphisms in cytochrome P450 and glutathione S-transferase genes and disease susceptibility in 106 patients with histologically proven squamous cell carcinoma of the oral cavity. The CYP2D6 PM phenotype was associated with a significantly increased risk of oral cancer (p = 0.0012). The CYP2D6 PM and HET phenotypes appear to be markers for a putative tumour suppressor gene at or close to 22q12. The EM phenotype is a risk factor in individuals who are heavy drinkers and smokers, possibly due to phase 1 activation of 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone