Role of CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 genes in the susceptibility to acute leukemias

Aydin-Sayitoglu M., Hatirnaz O., Erensoy N., Ozbek U.

AMERICAN JOURNAL OF HEMATOLOGY, cilt.81, ss.162-170, 2006 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 81
  • Basım Tarihi: 2006
  • Doi Numarası: 10.1002/ajh.20434
  • Dergi Adı: AMERICAN JOURNAL OF HEMATOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.162-170
  • Anahtar Kelimeler: CYP2D6, CYP1A1, CYP2E1, GSTT1, GSTM1, acute leukemia, ACUTE LYMPHOBLASTIC-LEUKEMIA, DNA ADDUCT LEVELS, ACUTE MYELOID-LEUKEMIA, S-TRANSFERASE M1, DRUG-METABOLIZING-ENZYMES, ADULT ACUTE-LEUKEMIA, WHITE BLOOD-CELLS, CANCER SUSCEPTIBILITY, TURKISH POPULATION, MOLECULAR EPIDEMIOLOGY
  • İstanbul Üniversitesi Adresli: Evet

Özet

Acute leukemias (ALs) are heterogeneous diseases. Functional polymorphisms in the genes encoding detoxification enzymes cause inter-individual differences, which contribute to leukemia susceptibility. The CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 polymorphisms in ALL (n = 156) and AML (n = 94) patients and 140 healthy controls were genotyped by PCR and/or PCR-RFLP using blood or bone marrow samples. No association was observed between the GSTT1 gene deletion and patients (OR = 0.8, 95% CI = 0.4-1.7 for AMLs and OR = 0.9, 95% CI = 0.5-1.6 for ALLs). Patients with ALL and AML had a higher prevalence of the GSTM1 deletions compared to controls but only the difference among adult AML patients (OR = 2.1, 95% Cl = 1.0-4.2) was statistically significant. The CYP2D6*3 variant allele frequency was lower in the overall acute leukemia patients (0.6%) compared to controls (P = 0.03). CYP2D6*1/*3 genotype frequency also showed a protective association in AML patients (OR = 0.09, 95% Cl = 0.01-1.7; P = 0.04). We also found a risk association for CYP2E1*5 in ALL and AML (OR = 3.6, 95% Cl = 1.4-9.4 and OR = 3.9, 95% Cl = 1.4-10.5, respectively). No association was found for the studied CYP2D6*4, CYP1A1 *2A, and GSTT1 "null" variants and the risk of acute leukemia (ALL or AML). This case-control study suggests a contribution of CYP2E1, CYP2D6, and GSTM1 "null" variants to the development of acute leukemias.