CYP2 C9 polymorphism among patients with oral squamous cell carcinoma and its role in altering the metabolism of benzo[a]pyrene

Abstract

Objectives: The aim of this study was to evaluate the prevalence of CYP2 C9 polymorphism among healthy controls and patients with oral squamous cell carcinoma (OSCC) and to analyze the risk of disease development. We also investigated the interaction between CYP2 C9 wild type and the polymorphic variants with benzo[a]pyrene by using molecular docking analysis.

Study design: The study included 46 patients with OSCC and 46 controls. Amplification of the genomic DNA was done by using allele-specific polymerase chain reaction and then analyzed by using agarose gel electrophoresis. Molecular docking was then carried out to determine the interaction of CYP2 C9*1, CYP2 C9*2, and CYP2 C9*3 with benzo[a]pyrene.

Results: In the OSCC group, CYP2 C9*2 and CYP2 C9*3 polymorphisms were 17.4% and 15.2%, respectively, and in the control group, they were 8.7% and 6.5%, respectively. The OSCC group showed a statistically significant (P = .043) increase in the prevalence of CYP2 C9 polymorphic variants compared with the control group. The docking analysis showed benzo[a]pyrene to bind specifically to the altered single nucleotide catalytic site in the polymorphic CYP2 C9*3 enzyme.

Conclusions: This study demonstrates that functionally important CYP2 C9 polymorphism exists among patients with OSCC, with a modest increase in the risk of disease development in those individuals who acquire these poor metabolizing variants. The modified docking of CYP2 C9*3 with benzo[a]pyrene signifies altered metabolism in vivo.