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Role of CYP2D6, CYP1A1, CYP2E1, GSTT1 , and GSTM1 genes in the susceptibility to acute leukemias
Author(s) -
AydinSayitoglu Muge,
Hatirnaz Ozden,
Erensoy Nevin,
Ozbek Ugur
Publication year - 2006
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.20434
Subject(s) - gene , cyp2e1 , acute leukemia , medicine , genetics , biology , leukemia , cancer research , immunology , in vitro , microsome
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% CI = 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% CI = 0.01–1.7; P = 0.04). We also found a risk association for CYP2E1*5 in ALL and AML (OR = 3.6, 95% CI = 1.4–9.4 and OR = 3.9, 95% CI = 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 leuke‐mia (ALL or AML). This case‐control study suggests a contribution of CYP2E1 , CYP2D6 , and GSTM1 “null” variants to the development of acute leukemias. Am. J. Hematol. 81:162–170, 2006. © 2006 Wiley‐Liss, Inc.