Novel genetic biomarkers for susceptibility to oral submucous fibrosis: cytochrome P450 3A

Abstract

Oral submucous fibrosis (OSF) is a chronic and insidious oral mucosal disease, which always carries high risk of transition to oral cancer. Mainly based on genetic predisposition in pharmacokinetics for toxic substances of betel quid, there are obviously variable responses to betel quid among chewers. But the key genes resulting in interindividual variability in OSF development are still obscure. The cytochrome P450 3A (CYP 3A) gene family plays major roles in the oxidative metabolism of active endogenous and xenobiotic substrates, which is generally found polymorphic with variant alleles in different individuals and regarded as a major determinant of the interindividual variability in chemicals pharmacokinetics. Based on the specific property of CYP 3A, we consider this polymorphically expressed genotype could be a predictor of OSF susceptibility. Betel-quid chewers with lower level of CYP 3A expression might be more susceptible to toxicity of betel quid, resulting in higher risk of OSF lesion. Meanwhile, individuals at genetically high risk of OSF could be screened according to the genetic polymorphisms in some exclusive regions of the CYP 3A genes. By analyzing the polymorphisms of CYP 3A genes, we could differentiate interindividual variability for pharmacokinetics of betel-quid chewers, and then guide OSF therapy.