title: GSTM1, GSTT1, GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population: different pattern of squamous cell carcinoma and adenocarcinoma.
abstract: OBJECTIVE
  To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma (SCC) and esophageal adenocarcinoma (ADC) in a high risk area of northwest of France.
  
  
  METHODS
  A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP1A1*2C and GSTP1 exon 7 Val alleles, GSTM1*2/*2 and GSTT1*2/*2 null genotypes). A total of 79 esophageal cancer cases and 130 controls were recruited.
  
  
  RESULTS
  GSTM1*2/*2 and CYP1A1*1A/*2C genotype frequencies were higher among squamous cell carcinomas at a level close to statistical significance (OR = 1.83, 95% CI 0.88-3.83, P = 0.11; OR = 3.03, 95% CI 0.93-9.90, P = 0.07, respectively). For GSTP1 polymorphism, no difference was found between controls and cases, whatever their histological status. Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference (OR = 13.31, 95% CI 1.66-106.92, P<0.01).
  
  
  CONCLUSIONS
  In SCC, our results are consistent with the strong association of this kind of tumour with tobacco exposure. In ADC, our results suggest 3 distinct hypotheses: (1) activation of exogenous procarcinogens, such as small halogenated compounds by GSTT1; (2) contribution of GSTT1 to the inflammatory response of esophageal mucosa, which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis; (3) higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.
authors.affiliation: GRECAN-EA1772, UFR des Sciences Pharmaceutiques, Universite de Caen Basse-Normandie et Centre Francois Baclesse, Avenue du General Harris, 14076 Caen cedex 05, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abbas
authors.forename: Karine
authors.initials: K
authors.lastname: Delvinquiere
authors.forename: Mathilde
authors.initials: M
authors.lastname: Lechevrel
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebailly
authors.forename: Pascal
authors.initials: P
authors.lastname: Gauduchon
authors.forename: Guy
authors.initials: G
authors.lastname: Launoy
authors.forename: François
authors.initials: F
authors.lastname: Sichel
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D000217:Acyltransferases; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C043403:fatty acyl ethyl ester synthase