title: Interactions between Glutathione-S-Transferase M1, T1 and P1 polymorphisms and smoking, and increased susceptibility to esophageal squamous cell carcinoma.
abstract: BACKGROUND
  A complex of genetic and environmental factors is involved in carcinogenesis of the esophageal squamous cell carcinoma (ESCC). Glutathione-S-Transferases (GSTs) are phase-II enzymes playing role in detoxification of carcinogen electrophiles. Genetic polymorphisms of GSTM1, GSTT1 and GSTP1 in association with some environmental factors and their impact on esophageal cancer susceptibility were assessed in the Iranian population.
  
  
  METHODS
  Genomic DNA of peripheral blood leukocytes from 148 confirmed esophageal cancer cases and 137 healthy individuals as control group was assayed for restriction fragment length polymorphisms in the GSTP1 loci by PCR amplification followed by digestion with Alw26I. Deletion of the GSTM1 and GSTT1 genes was detected by multiplex PCR. A data-mining method based on decision trees was applied to produce a predictive model of interactions between genotypes.
  
  
  RESULTS
  Smoking was independently associated with ESCC (p<0.05, OR: 2.286, 95% CI=1.311-3.983). Smoking along with GSTP1 Val/Val genotype was associated to ESCC (p<0.001, OR: 3.886, 95% CI=1.830-8.251), while non-smokers with GSTP1 Val/Val were significantly more frequent in non-cancerous group. (p=0.007, OR: 0.507, 95% CI=0.309-0.830).
  
  
  CONCLUSIONS
  Data-mining methods are useful tools to map out a scheme for predicting complex relations and combinations of different genotypes. Genotyping analysis of GSTP1 together with assessment of smoking seems to be important in determining the risk of ESCC in the Iranian population.
authors.affiliation: Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Omeed
authors.initials: O
authors.lastname: Moaven
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Raziee
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Sima
authors.forename: Azita
authors.initials: A
authors.lastname: Ganji
authors.forename: Reza
authors.initials: R
authors.lastname: Malekzadeh
authors.forename: Azadeh
authors.initials: A
authors.lastname: A'rabi
authors.forename: Abbas
authors.initials: A
authors.lastname: Abdollahi
authors.forename: Bahram
authors.initials: B
authors.lastname: Memar
authors.forename: Masoud
authors.initials: M
authors.lastname: Sotoudeh
authors.forename: Hossein
authors.initials: H
authors.lastname: Naseh
authors.forename: Navid
authors.initials: N
authors.lastname: Nekoui
authors.forename: Adeleh
authors.initials: A
authors.lastname: Razavipour
authors.forename: Mehran
authors.initials: M
authors.lastname: Gholamin
authors.forename: Ezzat
authors.initials: E
authors.lastname: Dadkhah
authors.forename: Moein
authors.initials: M
authors.lastname: Farshchian
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Abbaszadegan
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics; D003663:Decision Trees; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1