Association of cytochrome P450 2C9 polymorphism with locally advanced head and neck squamous cell carcinoma and response to concurrent cisplatin-based radical chemoradiation

Abstract

Aims: The aim of the present study is to investigate the association between polymorphism of cytochrome P450 2C9 (CYP2C9) enzyme with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving cisplatin-based radical chemoradiation (CT-RT). Materials and Methods: Four hundred and sixty patients suffering from locally advanced HNSCC and an equal number of healthy controls were genotyped for CYP2C9FNx012 and CYP2C9FNx013, leading to poor metabolizers (PMs) by polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP). Each case was assessed thoroughly for treatment response as per the World Health Organization (WHO) criteria. Results and Analysis: The frequency of heterozygous genotypes of both CYP2C9FNx012 (27.8%) and CYP2C9FNx013 (25%) were found to be significantly higher in the HNSCC cases as compared to the healthy controls. Tobacco intake in the form of chewing or smoking and alcohol intake resulted in several folds increase in the risk to HNSCC in the cases carrying variant genotypes of CYP2C9FNx012 or CYP2C9FNx013. Further, majority of the cases assessed for response (n = 436) carrying variant alleles of CYP2C9FNx012 (69.6%) or CYP2C9FNx013 (65.2%) were found to respond poorly to cisplatin-based radical CT-RT. Conclusion: The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome underlining the importance of pretherapeutic genotyping in determining the treatment protocol.

Keywords

• Chemoradiation
• CYP2C9
• head and neck cancer
• poor metabolizers
• treatment response