Cytochrome P450s (CYPs) play significant role in cancer formation and treatment outcome. CYP2C19 is involved in detoxification/inactivation of potential carcinogen(s) to reactive DNA binding metabolites such as nitrosamines and is also involved in the metabolism of several drugs. Therefore, polymorphic variations in CYP2C19 may lead to inappropriate metabolism of toxicants and variation in treatment outcome. Therefore, present case control study aims to investigate the association between G681A & G636A variants (alleles *2 & *3) of CYP2C19 gene, which accounts for enzyme's poor metabolism with susceptibility to oral cancer and treatment response.
350 patients suffering from oral cancer and equal number of age matched controls were included in the study. Genomic DNA was isolated from the blood samples and CYP2C19 genotypes were determined in genomic DNA by PCR based RFLP. Follow-up carried out to correlate the association (if any) in between variants and treatment outcome.
The frequency of variant alleles of CYP2C19 was found to be significantly higher in the cases when compared to the controls. Cigarette smoking and tobacco chewing significantly increased the risk of oral cancer in patients. A higher number of non-responders to chemo-radiotherapy were encountered during in patients carrying variant genotype during the follow up.
Our data indicate that cases with variant genotypes of CYP2C19 are susceptible to oral cancer. Increased risk amongst the smokers and tobacco chewers in cases indicate the interaction of CYP2C19 genotype with tobacco in developing oral cancer. This study further suggest that the presence of the inactive CYP2C19*2/*3 causes a reduction in the metabolic activation of anticancer agents, thereby lowering the risk of toxicity but worsening the therapeutic response. Further research into cytochrome P450 2C19 may provide more insights that will aid in the development of immunotherapy for oral cancer.
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All authors have declared no conflicts of interest.