title: Genetic polymorphisms of CYP2E1, GST, and NAT2 enzymes are not associated with risk of breast cancer in a sample of Lebanese women.
abstract: Changes in the activity of drug metabolizing enzymes (DMEs) are potentially associated with cancer risk. This relationship is attributed to their involvement in the bioactivation of multiple procarcinogens or the metabolism of multiple substrates including an array of xenobiotics and environmental carcinogens. 326 Lebanese women of whom 99 were cancer free (controls) and 227 were diagnosed with breast cancer (cases) were included. Blood for DNA was collected and medical charts were reviewed. Three genotyping methods were employed including: (1) restriction fragment length polymorphism (RFLP) for CYP2E1*5B, CYP2E1*6, NAT2*5 and NAT2*6; (2) gel electrophoresis for GSTM1 and GSTT1; and (3) real-time PCR for GSTP1 Ile/Val polymorphism. We analyzed the relationship between genetic susceptibilities in selected xenobiotic metabolizing genes and breast cancer risk. Allele frequencies were fairly similar to previously reported values from neighboring populations with relevant migration routes. There were no statistically significant differences in the distribution of variant carcinogen metabolizing genes between cases and controls even after adjusting for age at diagnosis, menopausal status, smoking, and alcohol intake. Despite its limitations, this is the first study that assesses the role of genetic polymorphisms in DMEs with breast cancer in a sample of Lebanese women. Further studies are needed to determine the genetic predisposition and gene-environment interactions of breast cancer in this population.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Medicine, American University of Beirut, Lebanon. nk16@aub.edu.lb
authors.forename: Nathalie K
authors.initials: NK
authors.lastname: Zgheib
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Shamseddine
authors.forename: Eddy
authors.initials: E
authors.lastname: Geryess
authors.forename: Arafat
authors.initials: A
authors.lastname: Tfayli
authors.forename: Ali
authors.initials: A
authors.lastname: Bazarbachi
authors.forename: Ziad
authors.initials: Z
authors.lastname: Salem
authors.forename: Ali
authors.initials: A
authors.lastname: Shamseddine
authors.forename: Ali
authors.initials: A
authors.lastname: Taher
authors.forename: Nagi S
authors.initials: NS
authors.lastname: El-Saghir
mesh_terms: D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001711:Biotransformation / Q000235:genetics*; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000208:ethnology / Q000235:genetics*; D018275:Carcinoma, Lobular / Q000208:ethnology / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004967:Estrogens; D005260:Female; D005787:Gene Frequency; D018734:Genes, erbB-2; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007861:Lebanon / Q000453:epidemiology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009376:Neoplasms, Hormone-Dependent / Q000208:ethnology / Q000235:genetics; D011110:Polymorphism, Genetic; D011374:Progesterone; D012307:Risk Factors
chemical_list: D001191:Arylamine N-Acetyltransferase; D019392:Cytochrome P-450 CYP2E1; D004967:Estrogens; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D009363:Neoplasm Proteins; D011374:Progesterone; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human