Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Therapy-related acute myeloid leukaemia/myelodysplastic syndrome (t-AML/t-MDS) results from an impaired ability to detoxify chemotherapeutic drugs or repair drug-induced genetic damage caused by genetic polymorphisms in enzymes involved in the metabolism of drugs. We analysed the prevalence of genetic polymorphisms of CYP1A1*2A(T6235C), CYP2E1*5B(C-1019T), CYP3A4*1B(A-290G), del{GSTT1}, del{GSTM1}, NQO1*2(C609T), MTHFR(C677T) and TYMS 2R/3R in 78 t-AML/t-MDS and 458 normal individuals (control group, CG) using real-time and conventional polymerase chain reaction (PCR)-based methods. The incidences of polymorphisms among t-AML/t-MDS patients and CG individuals were similar. However, a polymorphism profile consisting of CYP1A1*2A, del{GSTT1} and NQO1*2 strongly modified the risk of t-AML/t-MDS. The absence of all three polymorphisms decreased the risk of t-AML/t-MDS 18-fold (odds ratio (OR) = 0.054, 95% confidence interval (CI) = 0.005-0.63, P = 0.02), whereas the presence of only NQO1*2 or all three polymorphisms enhanced the risk of t-AML/t-MDS (OR = 2.09, 95% CI = 1.08-4.03, P = 0.03 and OR = 18.42, 95% CI = 1.59-212.76, P = 0.02 respectively). Thus, the profiles of genetic polymorphisms of drug-metabolising enzymes might explain the increased risk to t-AML/t-MDS observed in some patients treated with polychemotherapy.
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PMID:Profile of polymorphisms of drug-metabolising enzymes and the risk of therapy-related leukaemia. 1736 11

Several genetic polymorphisms in the genes coding folate-metabolizing enzymes have been associated with susceptibility to hematology malignancies. We conducted a Korean population-based case-control study to examine the relationship between the polymorphisms of folate-metabolizing enzymes and the risk of AML (acute myelogenous leukemia), CML (chronic myelogenous leukemia), MDS (myelodyspastic syndrome), and ALL (acute lymphoblastc leukemia). The MTHFR 677TT genotype was associated with an increased risk for ALL (odds ratios (OR)=1.77; 95% confidence intervals (CI)=1.02-3.09, p=.044). The MTRR 66 AG genotype was associated with an increased risk for MDS (OR=1.59; 1.06-2.38, p=.026) and the MTRR 66 GG genotype was associated with increased risk for AML (OR=1.51; 1.03-2.23, p=.037). The TYMS 2R3R genotype was associated with a decreased risk for AML (OR=0.76; 0.60-0.96, p=.022). The TYMS hap3 (2R-6bp) and hap4 (2R-0bp) were associated with decreased risk (OR=0.69; 0.53-0.90, p=.006) and increased risk (OR=1.65; 1.20-2.27, p=.002), respectively for AML. Hap C (677T-1298A) was associated with an increased risk (OR=1.40; 1.02-1.92, p=.04) for ALL. The risk for ALL appears to be associated with the MTHFR 677 polymorphism. The results are supportive of a risk modification by folate polymorphisms in several hematologic malignancies in Korea. The pattern of results suggests that MDS was associated with the DNA methylation status and the risk for AML was associated with both the DNA synthesis and DNA methylation status.
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PMID:Association between polymorphisms of folate-metabolizing enzymes and hematological malignancies. 1877 70