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.
Duarte
Eliza Carla Barroso
EC
Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Ribeiro
Daniela Cotta
DC
Gomez
Marcus Vinícius
MV
Ramos-Jorge
Maria Letícia
ML
Gomez
Ricardo Santiago
RS
D001938:Brazil; D002273:Carcinogens / Q000378:metabolism*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007972:Leukoplakia, Oral / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012907:Smoking
D002273:Carcinogens; D019363:Cytochrome P-450 CYP1A1; D019392:Cytochrome P-450 CYP2E1; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1