title: CYP 2D6 polymorphism: a predictor of susceptibility and response to chemoradiotherapy in head and neck cancer.
abstract: OBJECTIVE
  A major problem in cancer pharmacology is the unpredictability of the outcome of therapy, both in terms of tumor response and host toxicity. Pharmacogenetic variability associated with the drug metabolizing enzyme systems is a major determinant of variations in these outcomes.
  
  
  METHODS
  A case-control study of 100 male cases of head and neck squamous cell carcinoma and equal number of healthy controls was conducted. Genomic DNA isolated from blood samples collected from controls and patients was studied by PCR-RFLP technique for CYP2D6 polymorphism. All patients received three cycles of cisplatinum-based sequential chemoradiotherapy.
  
  
  RESULTS
  The increased frequency of variant genotypes was associated with a statistically significant increase in the risk in the cases both in CYP2D6*4 and *10. The effect of interaction of the risk modifiers such as cigarette smoking or tobacco chewing or alcohol drinking with the CYP2D6 genotypes in the controls and patients was found to be significant. Response to therapy in patients with variant genotypes of CYP2D6 (CYP2D6*4 and CYP2D6*10) and treated with radio and chemotherapy regimen was poor.
  
  
  CONCLUSIONS
  Functional enzyme deficiencies due to polymorphism in CYPs are not only important in enhancing susceptibility to head and neck squamous cell carcinoma but also in determining chemotherapeutic response.
authors.affiliation: Department of Radiation Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India. pragyaonco@gmail.com
authors.forename: Pragya
authors.initials: P
authors.lastname: Shukla
authors.forename: Deepak
authors.initials: D
authors.lastname: Gupta
authors.forename: Mohan Chand
authors.initials: MC
authors.lastname: Pant
authors.forename: Devendra
authors.initials: D
authors.lastname: Parmar
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D019389:Cytochrome P-450 CYP2D6