title: Genetic polymorphisms of glutathione S-transferase genes and susceptibility to colorectal cancer: a case-control study in an Indian population.
abstract: BACKGROUND
  Susceptibility to sporadic colorectal cancer is multifactorial and arises from interactive combinations of allelic variants in low-penetrance genes and relevant environmental risk factors. Genetic polymorphisms in metabolic enzymes as gene susceptibility factors may modify colorectal cancer risk. We evaluated the risk of colorectal cancer associated with respective or combined glutathione S-transferase (GST) polymorphisms and assessed the interactions between genes and environmental factors in a case-control study in an Indian population.
  
  
  METHODS
  The study included 59 colon and 243 rectal cancer cases, and 291 cancer-free healthy controls. GST genotypes were detected by multiplex PCR-based and PCR-RFLP methods. The risk of cancer associated with GST polymorphisms was estimated by calculation of odds ratios (ORs) and confidence intervals (95% CIs) using unconditional logistic regression.
  
  
  RESULTS
  The GSTM1 null genotype was found to be associated with a significantly increased rectal cancer risk (OR=1.55; 95% CI, 1.05-2.30), while the GSTT1 null genotype with a greater risk of colon cancer (OR=2.15; 95% CI, 1.04-4.32). A substantial increase of both colon (OR=10.81; 95% CI, 1.11-107.22) and rectal (OR=4.80; 95% CI, 0.94-35.91) cancer risk was shown for the combination of GSTM1 null, GSTT1 null and GSTP1 105Val allele. The combined GSTM1 null and GSTP1 114Val allele also revealed an increased risk for either colon cancer (OR=4.69; 95% CI, 0.84-23.87) or rectal cancer (OR=5.68; 95% CI, 1.79-22.16). Furthermore, the combination of GSTM1 null, GSTT1 null and GSTP1 114Val allele was found in 2 rectal cancer cases.
  
  
  CONCLUSIONS
  Our results suggest that co-exist of GSTM1 null, GSTT1 null and the variant GSTP1 105Val or 114Val allele may be predisposing risk factors for colorectal cancer in Indian population.
authors.affiliation: Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. wjw@med.nagoya-cu.ac.jp
authors.forename: Jingwen
authors.initials: J
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Vendhan
authors.initials: V
authors.lastname: Gajalakshmi
authors.forename: Kiyonori
authors.initials: K
authors.lastname: Kuriki
authors.forename: Sadao
authors.initials: S
authors.lastname: Suzuki
authors.forename: Teruo
authors.initials: T
authors.lastname: Nagaya
authors.forename: Seiichi
authors.initials: S
authors.lastname: Nakamura
authors.forename: Susumu
authors.initials: S
authors.lastname: Akasaka
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Shinkan
authors.initials: S
authors.lastname: Tokudome
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012004:Rectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012007:Rectum / Q000378:metabolism; D012307:Risk Factors; D055815:Young Adult
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human