Association and treatment response to capecitabine-based chemoradiotherapy with CYP2C9 polymorphism in head and neck cancer

Abstract

The aim of the present study is to investigate the association of polymorphism in cytochrome P450 2C9 (CYP2C9) with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving chemoradiotherapy. One hundred ten males suffering from locally advanced head and neck squamous cell carcinoma and an equal number of healthy controls were genotyped for CYP2C9FNx012 and CYP2C9FNx013, leading to poor metabolizers (PMs) by PCR-based RFLP. Each case was assessed thoroughly for treatment response following WHO criteria. The frequency of heterozygous genotypes of both CYP2C9FNx012 (27.3%) and CYP2C9FNx013 (20.1%) 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 fold increase in the risk to HNSCC in the cases carrying variant genotypes of CYP2C9FNx012 or CYP2C9FNx013. Further, majority of the cases assessed for response (134) carrying variant alleles of both CYP2C9FNx012 (65.3%) or CYP2C9FNx013 (70.58%) were found to respond poorly to the radio-chemotherapy. 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 schedule.