title: Influence of CYP1A1, GST polymorphisms and susceptibility risk of chronic myeloid leukemia in Syrian population.
abstract: In the present study, we investigated the associations of polymorphisms in cytochrome P450 gene (CYP1A1), glutathione S-transferase genes (GSTM1 and GSTT1) with chronic myelogenous leukemia (CML). A total of 126 patients with CML and 172 healthy volunteers were genotyped, and the DNA was isolated from their blood samples. The polymorphisms were assessed by polymerase chain reaction (PCR) restriction fragment length polymorphism-based methods and multiplex PCR. Logistic regression analyses showed significant risk of CML associated with CYP1A1 Val allele [odds ratio (OR) 3.3, 95% confidence intervals (CI) 1.96-5.53], (p < 0.0001) while CYP1A1 Val/Val homozygotes were observed only in the CML patients. There was statistically significant difference in the frequency of GSTM1 and GSTT1 null genotypes. The GSTT1-null genotype was slightly higher in 27% of CML cases and 16.7% of controls (OR 1.98, 95% CI 1.12-3.5) (p < 0.020). The GSTM1 null was higher in 42.8% of CML cases and 22.7% of controls (OR 2.55, 95% CI 1.54-4.22) (p < 0.00024). The individuals carrying CYP1A1 Ile/Val (AG) and GSTM1 null genotype have 9.9 times higher risk to be CML than those carrying CYP1A1 Ile/Ile (AA) and GSTM1 present genotype (OR 9.9, 95% CI 2.7-36.3) (p < 0.0001). This suggests that the association of the GSTM1 null genotype, either alone or in combination with GSTT1 null, with CYP1AI heterozygous leads to the CML risk.
authors.affiliation: Human Genetics Division, Department of Molecular Biology and Biotechnology, Atomic Energy Commission of Syria, 17th Nissan St., Kafersouseh, 6091, Damascus, Syria, ascientific@aec.org.sy.
authors.forename: Walid
authors.initials: W
authors.lastname: Al-Achkar
authors.forename: Ghassan
authors.initials: G
authors.lastname: Azeiz
authors.forename: Faten
authors.initials: F
authors.lastname: Moassass
authors.forename: Abdulsamad
authors.initials: A
authors.lastname: Wafa
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics; D005006:Ethnicity; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012307:Risk Factors; D013593:Syria / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor; D019363:Cytochrome P-450 CYP1A1; D004247:DNA; D005982:Glutathione Transferase; C569463:CYP1A1 protein, human; C413545:glutathione S-transferase T1