title: Genetic polymorphisms in GSTM1, GSTT1 and GSTP1 genes and risk of lung cancer in a North Indian population.
abstract: BACKGROUND
  A number of studies done so far in different populations have shown that polymorphisms within the GST genes play an important role in determining individual susceptibility to lung cancer; however, data obtained so far have been contradictory within the same or different populations. Few studies have focused on the combinatorial effect of the GST genes on susceptibility to lung cancer and also for different histological subtypes. Our aim is to investigate the roles of GSTM1, GSTT1, and GSTP1 polymorphisms as genetic modifiers of risk for lung cancer and histological subtypes using a larger sample size in a North Indian population.
  
  
  METHODS
  In total 540 subjects (270 lung cancer cases and 270 controls) were evaluated for the GST polymorphism. Genotyping for the GSTM1, GSTT1 and GSTP1 gene was done by using a multiplex PCR and PCR-RFLP method.
  
  
  RESULTS
  GSTM1 null genotype was found to be associated with lung cancer (OR=1.65, 95%CI: 116-2.3, P=0.005) and this risk was higher in cases of adenocarcinoma (ADCC). GSTT1 and GSTP1 did not show any significant association with lung cancer; however, when stratified for histological subtypes a significant association was observed for ADCC and small-cell lung cancer (SCLC) for both GSTT1 null and variant GSTP1 genotypes. The combined 'at risk' genotypes of null GSTM1 and GSTT1 genes were found to be associated with lung cancer risk, and this risk was higher in cases of ADCC (OR=4.09, 95%CI: 110-10.2, P=0.002). There is a twofold increased risk for lung cancer with the null GSTM1 and wild-type GSTP1 genotypes (P=0.0004); similarly, a fourfold increased risk was observed with the null GSTT1 and wild-type GSTP1 genotypes (P=0.0001).
  
  
  CONCLUSIONS
  The deficient GST genotypes seem thus to be important risk modifiers for lung cancer and related histological subtypes, especially in combination.
authors.affiliation: Department of Biotechnology, Thapar University, Patiala, Punjab 147002, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Department of Biotechnology, Thapar University, Patiala, Punjab 147002, India.
authors.forename: Amrita
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Pulmonary Medicine, Post Graduate Institute of Education and Medical Research (PGIMER), Sector 14, Chandigarh, India.
authors.forename: Navneet
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Pulmonary Medicine, Post Graduate Institute of Education and Medical Research (PGIMER), Sector 14, Chandigarh, India.
authors.forename: Digamber
authors.initials: D
authors.lastname: Behera
authors.affiliation: Department of Biotechnology, Thapar University, Patiala, Punjab 147002, India. Electronic address: siddharthsharma.phd@thapar.edu.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; 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; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1
keywords: @ GSTM1; GSTP1; GSTT1; Genotype; Lung cancer; Polymorphism