Role of Genetic Variations in Determining Treatment Outcome in Head and Neck Cancer

Abstract

Worldwide, head and neck squamous cell carcinoma (HNSCC) is responsible for >550,000 diagnoses and 380,000 deaths annually. It originates in the upper aerodigestive tract and has a multifactorial origin involving both genetic and lifestyle risk factors. The clinical management of HNSCC involves surgery, radiotherapy, and chemotherapy. Several studies point to the role of genetic variations in predicting drug efficacy and toxicity. Cancer pharmacogenomics has fast emerged as a new and promising field for the early identification of genetic markers that can predict drug response or toxicity, with the number of studies of genetic polymorphisms as prognostic factors of HNSCC treatment outcomes growing. The number of studies evaluating the association of candidate polymorphisms in drug-metabolising Phase I and II enzymes with treatment outcome far exceed the studies involving other candidate genes, such as those involved in drug metabolism, DNA repair, and cell cycle regulation. This review focusses on the relevance of genetic variations in genes, where the corresponding gene products play an important role in drug metabolism (TPMT, DPD), DNA repair (X-ray repair cross complementing 1), cell cycle (tumour protein P53), and carcinogenesis (matrix metalloproteinase 3 and 7), thereby contributing to the treatment outcome for HNSCC. This could greatly help clinicians in identifying genetic markers useful for the selection of optimal drugs, dose, and treatment duration on an individual basis, resulting in improved drug efficacy and decreased toxicity. However, further studies are needed in well characterised and larger HNSCC populations with proper validation of pharmacogenetic markers in experimental settings before application in clinical routine diagnostics.