Much of the inter-individual differences in the regulation, expression, and activity of drug metabolizing enzymes genes might be crucial factors in defining cancer susceptibility, as well as in determining the efficacy of drugs. Cytochrome P450 (CYP) family of enzymes are the most important drug metabolizing enzymes involved in the metabolism of widely used drugs including anticancer drugs like tamoxifen and cyclophosphamide. Therefore, present study was undertaken to investigate the association of variant genotypes of CYP2C9, CYP2C19 & CYP2D6 with the treatment response (personalized medicine approach) in Head and Neck cancer cases receiving chemotherapy or combination of chemo- and radiotherapy.
800 patients suffering from Head & Neck cancer and equal number of age matched controls were included in the study. Genomic DNA was isolated from the blood samples and CYP2C9, CYP2C19 & CYP2D6 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.
Amongst heterozygous and homozygous variants of CYP2C9*2/*3; CYP2C19*2 /*3 (i.e. CYP2C9*1/*2, CYP2C9*1/*3, CYP2C19*1/*2 & CYP2C19*1/*3) and CYP2D6*4/*10, a high percentage of cases was encountered as non-responders and had toxicities like nausea, vomiting, dizziness etc., as compared to the responders in the same category. In the follow-up study, it was found that a significantly higher number of non-responders (p-value<0.05) were encountered in the cases carrying variant genotypes of either of CYP2C9*2, CYP2C9*3, CYP2C9*2/*3, CYP2C19*2, CYP2C19*3, CYP2C19*2/*3, CYP2D6*4 and CYP2D6*10.
It was demonstrated that CYP2C9, CYP2C19 and CYP2D6 variants modify the treatment outcome in cases receiving combination of radio-chemotherapy.
Clinical trial identification
Legal entity responsible for the study
Government of India.
Has not received any funding.
All authors have declared no conflicts of interest.