Genetic polymorphisms of carcinogen metabolizing enzymes are associated with oral leukoplakia development and p53 overexpression.

BACKGROUND

Genetic polymorphisms of carcinogen-metabolizing enzyme genes have been associated with the risk of oral squamous cell carcinoma and oral leukoplakia. The overexpression of p53 protein is the most common genetic alteration in head and neck cancer. In the present study the combined or isolated presence of glutathione S-transferases GSTM1, GSTT1, GSTP1, and the cytochrome P450 oxidases CYP1A1 and CYP2E1 polymorphisms and oral leukoplakia development in a Brazilian sample of individuals was investigated, together with the effect of these polymorphisms on p53 overexpression in the lesions.

METHODS

The GSTM1, GSTT1 and CYP1A1 genotypes of 80 smoking patients with oral leukoplakia and 80 age and gender matched control subjects were studied by polymerase chain reaction (PCR), and CYP2E1 and GSTP1 polymorphisms by PCR and digestion. Immunohistochemical reactions were performed for p53 staining in paraffin embedded histological sections of oral leukoplakia lesions.

RESULTS

The GSTM1 null genotype was associated with an increased risk of oral leukoplakia development, independently of the other genes (OR 2.10). The simultaneous presence of GSTM1 and GSTT1 null genotypes was associated with an increased risk of oral leukoplakia development, independently of the other genes (OR 4.36). The oral leukoplakia lesions of patients with the GSTT1 null genotype showed a 6-fold increased risk of p53 overexpression (OR 6.61).

CONCLUSIONS

A positive association exists between the isolated or combined null genotype of GSTM1 and GSTT1 and oral leukoplakia development and the null GSTT1 genotype shows increased risk of p53 overexpression, in oral leukoplakia.