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Cytochrome P450 and Glutathione Transferase Expression in Squamous Cell Cancer

Karmanos Cancer Institute, Wayne State University, Detroit, Michigan

Purpose: The cytochrome P-450 (CYP) and glutathione S-transferase (GST) enzyme systems modulate the carcinogenic effects of tobacco. Therefore, the expression of these enzymes may be in part responsible for the observed interindividual and inter-racial differences in the risk of development of squamous cell carcinoma of the head and neck (SCCHN). The first aim of this study was to evaluate the feasibility of measuring the expression of the CYP and GST in target tissue from the head and neck. The second aim was to compare the expression of CYPs 1A1, 2E1, and 3A4 in squamous epithelium from African-American and Caucasian pediatric patients. The third aim was to compare the expression of CYPs 1A1, 2E1, 3A4, and GST- on the p16 expression in patients with SCCHN.

Experimental Design: The expression of CYP 1A1, 2E1, 3A4, GST-, and p16 was quantified by immunoblotting. Expression of CYPs 1A1, 2E1, and 3A4 was quantified in tissue from 160 pediatric patients undergoing tonsillectomy. Expression of CYPs 1A1, 2E1, 3A4, GST-, and p16 was determined in 46 resected SCCHN patients.

Results: Large interindividual variability in the expression of these enzymes was observed in the pediatric and adult populations. No significant difference was observed in CYP 1A1, 2E1, and 3A4 expression of Caucasian and African-American patients. There was no correlation between p16 and enzyme expression in patients with SCCHN.

Conclusion: Evaluation of CYP expression in the target tissue of interest is feasible. The clinical significance of CYPs and GST- alterations in the risk of developing SCCHN will need to be investigated in larger trials.