title: No role for glutathione S-transferase genotypes in Caucasian esophageal squamous cell or adenocarcinoma etiology: an European case-control study.
abstract: BACKGROUND
  Identifying and monitoring high-risk patients can aid the prevention of esophageal cancer (EC). The interaction of environmental risk factor exposure and genetic susceptibility may contribute to the etiology of EC. Biotransformation enzymes such as Glutathione S-Transferases (GSTs ) detoxify mutagenic and genotoxic compounds and therefore control the rate of detoxification of carcinogens. Functional polymorphisms in the genes coding for GSTs alter their enzyme activity in vitro, and were reported to modify EC risk in Asians. We hypothesized that altered enzyme activity GST genotypes influence the susceptibility for esophageal adeno- (EAC) and squamous cell carcinoma (ESCC) in Caucasians.
  
  
  METHODS
  We performed a case-control study including 440 Caucasian patients with EC and 592 healthy Caucasian controls matched for age and sex. Functional polymorphisms were selected and genotypes were determined in GST classes Alpha, Mu, Theta and Pi by means of polymerase chain reaction. Genotypes were classified into predicted high, intermediate and low enzyme activity categories based on in vitro activity data. The distribution of the activity genotypes were compared between patients with EAC or ESCC, and controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by logistic regression analyses. Gene-gene interactions were tested and for comparison purposes, the predicted low and intermediate activity genotypes were combined. Genotypes with similar risks for EAC or ESCC were combined and analyzed for multiplicative effects.
  
  
  RESULTS
  Our analyses includes 327 patients with EAC and 106 patients with ESCC. Low or intermediate activity enzyme genotypes for GSTM1, GSTA1, GSTP1 I105V and A114V as well as for GSTT1, did not significantly modify the risk for ESCC or EAC in our Dutch population.
  
  
  CONCLUSIONS
  Functional genotypes in GST genes are not involved in EAC or ESCC susceptibility in Caucasians, in contrast to results on ESCC from Asia or Africa.
authors.affiliation: Department of Gastroenterology, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. p.dura@mdl.umcn.nl
authors.forename: Polat
authors.initials: P
authors.lastname: Dura
authors.forename: Jody
authors.initials: J
authors.lastname: Salomon
authors.forename: Rene H M
authors.initials: RH
authors.lastname: Te Morsche
authors.forename: Hennie M J
authors.initials: HM
authors.lastname: Roelofs
authors.forename: Jon O
authors.initials: JO
authors.lastname: Kristinsson
authors.forename: Theo
authors.initials: T
authors.lastname: Wobbes
authors.forename: Ben J M
authors.initials: BJ
authors.lastname: Witteman
authors.forename: Adriaan C I T L
authors.initials: AC
authors.lastname: Tan
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.forename: Wilbert H M
authors.initials: WH
authors.lastname: Peters
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics*
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; C413545:glutathione S-transferase T1; C119995:glutathione S-transferase alpha