Polymorphisms in transporter and phase II metabolism genes as potential modifiers of the predisposition to and treatment outcome of de novo acute myeloid leukemia in Israeli ethnic groups.
Drug metabolism/disposition and transporter genes may influence predisposition or prognosis of AML (acute myeloid leukemia) patients. We analyzed polymorphisms in 3 transporters and 4 drug metabolism genes in 293 Israeli individuals (112 AML patients and 181 controls). We analyzed: ABCC3 (MRP3) C-211T; ABCG2 (BCRP) C421A; CNT1 (SLC28A1) G565A and NAT1, NAT2, and GSTT1 and GSTM1 null alleles for influence on predisposition, as well as treatment response and survival. We found that the ABCC3 C-211T polymorphism and GSTM1 null genotype have adverse prognostic significance in AML. None of the other polymorphisms studied were found to influence either predisposition or prognosis in Israeli AML patients.
Müller
Phillip
P
German Cancer Research Center DKFZ, Division of Toxicology and Cancer Risk Factors, Heidelberg, Germany.
Asher
Nava
N
Heled
Maya
M
Cohen
Sara Bar
SB
Risch
Angela
A
Rund
Deborah
D
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D007557:Israel / Q000453:epidemiology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001191:Arylamine N-Acetyltransferase; D014408:Biomarkers, Tumor; D017931:DNA Primers; D005982:Glutathione Transferase; D007527:Isoenzymes; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C116614:ABCG2 protein, human; C065171:cif nucleoside transporter; C114462:multidrug resistance-associated protein 3; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1