title: Genetic variation in carcinogen metabolizing genes associated with oral cancer in pakistani population.
abstract: BACKGROUND
  Xenobiotics are metabolized by either phase I enzymes like CYP1A1 or phase II enzymes like GSTs. Polymorphisms in the encoding genes (CYP1A1, GSTM1, GSTT1 and GSTP1) potentially may therefore contribute towards risk association for oral cancer.
  
  
  METHODS
  These genes were investigated via a case control study consisting of 228 oral cancer patients and 150 cancer free normal individuals as controls. DNA was extracted from WBCs for genotyping. Polymerase chain reaction-single stranded conformational polymorphism (SSCP) was used for screening CYP1A1 and GSTP1 genes mutations. Deletion of GSTM1 and GSTT1 genes were analyzed by multiplex PCR.
  
  
  RESULTS
  Two novel mutations were found in this study in relation to oral cancer. A substitution mutation of A2842 with C resulting in missense tyrosine to serine formation along with a frameshift mutation due to insertion of thymidine at nucleotide 2842 resulting in 495 nucleotide sequence to alter was found in oral cancer patients. GSTM1 and GSTT1 deletion polymorphism was found in significantly higher number of individuals (OR=2.08, CI 1.05-4.2; OR=1.5, CI 0.9-2.4 respectively) compared to controls. 10 patients had deletion of both GSTM1 and GSTT1 genes. GSTP1 gene was also found to have novel substitution mutations of A2848 to T and G2849 to A in exon 7 resulting in leucine to leucine and alanine to threonine formation respectively. Two intronic deletions of cytosine at positions 1074 and 1466 was found in intron 3 and 4 in patients and no control had these exonic or intronic variants in GSTP1 gene.
  
  
  CONCLUSIONS
  These results suggest that accumulation of genetic changes in CYP1A1, GSTM1, GSTT1 and GSTP1 genes are associated with increased risk of oral cancer.
authors.affiliation: Biosciences, COMSATS Institute of Information and Technology, Islamabad, Pakistan. nosheenmasood@hotmail.com
authors.forename: Nosheen
authors.initials: N
authors.lastname: Masood
authors.forename: Mahmood Akhtar
authors.initials: MA
authors.lastname: Kayani
authors.forename: Fraz Arshad
authors.initials: FA
authors.lastname: Malik
authors.forename: Ishrat
authors.initials: I
authors.lastname: Mahjabeen
authors.forename: Ruqia Mehmood
authors.initials: RM
authors.lastname: Baig
authors.forename: Rani
authors.initials: R
authors.lastname: Faryal
mesh_terms: D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010154:Pakistan; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis
chemical_list: D019363:Cytochrome P-450 CYP1A1; D004273:DNA, Neoplasm; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human