Premium
Profile of polymorphisms of drug‐metabolising enzymes and the risk of therapy‐related leukaemia
Author(s) -
Bolufer Pascual,
Collado Maria,
Barragan Eva,
Calasanz MaríaJosé,
Colomer Dolors,
Tormo Mar,
González Marcos,
Brunet Salut,
Batlle Montserrat,
Cervera José,
Sanz MiguelAngel
Publication year - 2007
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.06469.x
Subject(s) - odds ratio , medicine , methylenetetrahydrofolate reductase , cyp3a5 , myelodysplastic syndromes , gastroenterology , oncology , pharmacology , genotype , biology , bone marrow , genetics , gene
Summary 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 { GSTT 1}, del { GSTM 1}, 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 { GSTT 1} 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.