CYP1A1, CYP2E1, and GSTM1 gene polymorphisms and susceptibility to colorectal and gastric cancer among Lebanese

Genet Test Mol Biomarkers. 2011 Jun;15(6):423-9. doi: 10.1089/gtmb.2010.0206. Epub 2011 Mar 8.

Abstract

Mutations in the genes encoding enzymes involved in the metabolism of chemical carcinogens can significantly affect the risk of cell transformation and cancer development. The resident Lebanese population has experienced a sharp increase in cancer incidence within the last few years. The relationship between gene polymorphisms of metabolic enzymes and gastrointestinal (GI) cancer incidence was not previously investigated. The aim of this study was to investigate the relationship between CYP1A1, CYP2E1, and GSTM1 gene polymorphisms and GI cancer incidence among Lebanese. Blood and/or paraffin-embedded biopsy samples were collected from patients and healthy controls. The genotypes were determined by polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. The results of the present case-control study show that the studied Lebanese population generally resembles Caucasian populations with respect to the considered polymorphisms. Further, the GSTM1*0/*0 genotype is a significant risk factor for gastric (odds ratio = 4.1; 95% confidence interval: 1.2-14.5) and colorectal cancers (odds ratio = 3.8; 95% confidence interval: 1.7-8.5); on the other hand, CYP1A1*2A and CYP2E1*6 alone are not significantly associated with GI cancer development, although CYP1A1*2A was more frequent among patients. A remarkable and statistically significant 36.5-fold increase in the risk of gastric cancer was observed among patients with CYP1A1*2A/*2A combined with GSTM1*0/*0. The investigation of genetic risk factors and susceptibility gene polymorphisms in Lebanese is helpful for better understanding of GI cancer etiology.

MeSH terms

  • Aged
  • Case-Control Studies
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / genetics*
  • Cytochrome P-450 CYP1A1 / genetics*
  • Cytochrome P-450 CYP2E1 / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Glutathione Transferase / genetics*
  • Humans
  • Lebanon
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic*
  • Risk Factors
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / etiology
  • Stomach Neoplasms / genetics*

Substances

  • Cytochrome P-450 CYP2E1
  • Cytochrome P-450 CYP1A1
  • Glutathione Transferase
  • glutathione S-transferase M1