title: The 341C/T polymorphism in the GSTP1 gene is associated with increased risk of oesophageal cancer.
abstract: BACKGROUND
  The Glutathione S-transferases (GSTs) comprise a group of enzymes that are critical in the detoxification of carcinogens. In this study the effects of polymorphisms in these genes on the risk of developing oesophageal squamous cell carcinoma (OSCC) were evaluated in a hospital-based case-control study in two South African population groups. Genetic polymorphisms in GSTs were investigated in 245 patients and 288 controls samples by PCR-RFLP analysis.
  
  
  RESULTS
  The GSTP1 341T variant was associated with significantly increased risk of developing OSCC as observed from the odds ratios for the GSTP1 341C/T and GSTP1 341T/T genotypes (OR = 4.98; 95%CI 3.05-8.11 and OR = 10.9; 95%CI 2.43-49.1, respectively) when compared to the homozygous GSTP1 341C/C genotype. The risk for OSCC in the combined GSTP1 341C/T and T/T genotypes was higher in tobacco smokers (OR = 7.51, 95% CI 3.82-14.7), alcohol consumers (OR = 15.3, 95% CI 1.81-12.9) and those using wood or charcoal for cooking and heating (OR = 12.1, 95% CI 3.26-49) when compared to those who did not smoke tobacco, or did not consume alcohol or user other forms of fuel for cooking and heating. Despite the close proximity of the two GSTP1 SNPs (313A>G and 341C>T), they were not in linkage disequilibrium in these two population groups (D':1.0, LOD: 0.52, r2: 0.225). The GSTP1 313A/G polymorphism on the other hand, did not display any association with OSSC. The homozygous GSTT1*0 genotype was associated with increased risk of OSCC (OR = 1.71, 95%CI 1.18-2.46) while the homozygous GSTM1*0 genotype was associated with significantly decreased risk of OSCC in the Mixed Ancestry subjects (OR= 0.39, 95%CI 0.25-0.62).
  
  
  CONCLUSIONS
  This study shows that the risk of developing OSCC in the South African population can be partly explained by genetic polymorphisms in GST coding genes and their interaction with environmental factors such as tobacco smoke and alcohol consumption.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), UCT Campus, Anzio Road Observatory 7925, Cape Town, South Africa.
authors.forename: Dongping
authors.initials: D
authors.lastname: Li
authors.forename: Collet
authors.initials: C
authors.lastname: Dandara
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Parker
mesh_terms: D000428:Alcohol Drinking; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking; D013019:South Africa
chemical_list: D051549:Glutathione S-Transferase pi