Genetic polymorphism of drug metabolizing enzymes (GSTM1 and CYP1A1) as risk factors for oral premalignant lesions and oral cancer.
OBJECTIVE
Polymorphisms in the genes that code for metabolic enzymes involved in either the activation (Phase I) or detoxication (Phase II) of chemical carcinogens in tobacco, may alter expression or function of carcinogenic compounds and hence alter risk of oral cancer. The present study investigates whether polymorphisms at CYP1A1 and GSTM1 gene loci act as risk factors for oral precancerous lesions and cancer.


METHODS
For the present study, histopathologically confirmed cases of 90 oral precancerous lesions, 150 oral squamous cell carcinoma (SCC) and 150 control subjects were selected. Polymerase chain reaction and restriction fragment length polymorphism were performed using DNA from blood samples to determine the polymorphic genotypes at CYP1A1 and GSTM1 loci.


RESULTS
CYP1A1 C (m2/m2) genotype conferred a 12.0 fold-increased risk (OR=12.0; 95% CI, 2.40-60.05) to oral SCC. GSTM1 null showed no significant association but the frequency was higher in oral SCC cases. Patients with genotype C and/or GSTM1 deficiency developed carcinoma after less tobacco consumption than those of other genotypes though the difference was not statistically significant. The frequency of the combined genotypes C and GSTM1 null was found to be 14% among oral SCC patients. On comparing the susceptibility of intraoral sites it was found that in the majority of cases (64%) in the study groups they were the buccal mucosa.


CONCLUSIONS
Hence it was concluded that metabolic enzymes reported in the present study: CYP1A1 significantly alter oral cancer risk. GSTM1 null and CYP1A1 C (m2m2) show a predisposition to premalignant lesions and cancer of the buccal mucosa than other sites.
Department of Oral Pathology and Microbiology, Faculty of Dentistry, Jamia Millia Islamia, Delhi, India.
Deepika
D
Shukla
Alka
A
Dinesh Kale
Seema
S
Hallikerimath
Subbiah
S
Vivekanandhan
Yerrmalla
Y
Venkatakanthaiah
D000328:Adult; D002273:Carcinogens / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011230:Precancerous Conditions / Q000235:genetics*; D012307:Risk Factors
D002273:Carcinogens; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase