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INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH

A Step Towards Excellence
Published by : Advanced Scientific Research
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0975-2366
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IJPR 9[3] July - September 2017 Special Issue

July - September 9[3] 2017

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Mutation and gene expression analysis of Cytochrome P450 Family 1 to decipher the association with HNSCC

Author: PADMA N, SMILINE GIRIJA A.S, PARAMASIVAM A, VIJAYSHREE PRIYADHARSINI J
Abstract: Cytochrome P450s consist of a huge family of enzymes that catalyze the nicotine metabolism with a unique emphasis on the metabolism of tobacco based carcinogens. A few isoforms of this enzyme were found to convert procarcinogens to carcinogens, which results in the transformation of cells. The exposure to carcinogenic chemicals in tobacco is considered as an important risk factor of head and neck squamous cell carcinoma (HNSCC) which increases the risk by 5 - 25 folds. The present study aims to identify the gene alterations within the CYP2 family of cytochromes in HNSCC patients. The evaluation follows an observational study design, employing numerous computational tools to derive an association of the variants and alterations identified with HNSCC. The cBioportal server was used to predict the gene alterations followed by the PROVEAN, I-Mutant and gnomAD predictions. Several novel mutations and one reported single nucleotide variant (rs777515179) in CYP1B1 gene was identified. The protein stability analysis revealed that all the missense variants identified were found to decrease the protein stability, with a few exhibiting deleterious consequences. The gene expression profile was found to differ significantly among normal and different grades of HNSC tumor. Survival curve analysis also revealed that an increased expression in CYP1B1 gene in female patients was related to poor survival. Hence, the present study throws light on the possible association of variants in CYP1 family of genes with HNSCC.
Keyword: Cytochrome P450; HNSCC; In silico, mutations, amplification, deletions.
DOI: https://doi.org/10.31838/ijpr/2020.12.04.300
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