title: Expression of xenobiotic metabolizing genes in head and neck cancer tissues.
abstract: BACKGROUND
  Xenobiotic metabolizing genes are involved in detoxification of carcinogens. Expression of these enzymes may be one of the reasons for interindividual differences in head and neck cancer risks. The aim of current study was first to evaluate the expression of CYP1A1, GSTM1, GSTT1 and GSTP1 and second to observe its relationship with stages of head and neck cancer in Pakistani population.
  
  
  METHODS
  Fresh biopsy tissues were taken from oncology institutional hospitals. Semi quantitative reverse transcriptase polymerase chain reaction was used to investigate CYP1A1, GSTM1, GSTT1 and GSTP1 expression in 49 head and neck cancer tumor tissue and 49 normal healthy tissues. Statistical analysis was performed to explore its association with head and neck cancer risk.
  
  
  RESULTS
  The current study revealed that the CYP1A1 mRNA expression was markedly reduced in tissues of head and neck carcinoma compared to adjacent normal tissue (OR 4.5, CI 1.5-13.4). CYP1A1 expression was downregulated in 62.5% tissues of stage 1, 72.7% tissues of stage 2, 60% tissues of stage 3 and 100% tissues of stage 4. Undetectable or partial loss of expression of GSTM1 and GSTT1 mRNA was also observed at a higher rate in head and neck cancer tissue compared to control (OR 4.5, CI 1.5- 13.4 and OR 3.2, CI 1.1- 9.6 respectively). GSTM1 and GSTT1 expression was also downregulated in stage wise pattern; stage 1 had 50% and 12.5% tissues showing down regulation of GSTM1 and GSTT1 genes respectively, both GSTM1 and GSTT1 had 55% tissues with down regulation in stage 2, similarly stage 3 had 60% tissues showing down regulation of these genes and stage 4 had 86% and 71% tumors. GSTP1 mRNA expression was significantly higher in cancer tissue as in control tissue (OR 4.2, CI 1.2- 15.3). GSTP1 over expression also revealed related to stages with 36.4%, 60% and 71% tumor of stage 2, 3 and 4 respectively.
  
  
  CONCLUSIONS
  Our results revealed that CYP1A1, GSTM1 and GSTT1 are downregulated in the head and neck cancer progression while GSTP1 is upregulated. These down regulations and up regulation were more marked in advanced stages of head and neck cancer. Therefore, CYP and GST expression may be an important mechanism involved in the carcinogenesis but the underlying mechanisms leading to such regulations in expression deserve further investigations.
authors.affiliation: COMSATS Institute of Information and Technology, Islamabad, Pakistan.
authors.forename: Nosheen
authors.initials: N
authors.lastname: Masood
authors.forename: Fraz Arshad
authors.initials: FA
authors.lastname: Malik
authors.forename: Mahmood Akhtar
authors.initials: MA
authors.lastname: Kayani
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019363:Cytochrome P-450 CYP1A1; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D012333:RNA, Messenger; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human