Aberrations in genes coding for cytochrome P450 family 2 and its putative association with HNSCC.

Abstract

Cytochrome P450s include a large family of enzymes that catalyze the nicotine metabolism with a special emphasis on the metabolism of tobacco specific carcinogens. A few isoforms of this enzyme were found to activate procarcinogens to active carcinogens. One of the important risk factors of head and neck squamous cell carcinoma (HNSCC) is smoking which increases the risk by 5 to upto 25 folds. The present study aims to assess the gene alterations in the CYP2 family of cytochromes so as to derive an association with HNSCC. The analysis follows an observational study design, employing several computational tools to identify and predict the possible outcomes of gene alterations identified in HNSCC patients. cBioportal server was used to identify the gene alterations which was further analysed using tools such as PROVEAN, I-Mutant and gnomAD. A total of 37 genes of the CYP2B family were analyzed, among which 19 genes were identified to harbour gross abnormalities and variations. Polymorphisms in the CYP genes may be associated with diseases and adverse drug reactions. The highest frequency of gene alteration was identified in the gene CYP2AB1P (21%) followed by CYP2R1 (2.8%) and CYP2W1 (2.6%). Gene amplification was a common observation with single nucleotide variations including both synonymous and truncating variants. Several reported polymorphic variants were also identified. The gene alterations identified in the present studied predicted the pathogenicity and protein stability at standard biological conditions. Further experimental studies would provide concrete evidence on the association of observed genetic abnormalities with HNSCC especially in individuals exposed to habitual carcinogens.