Increased risk of acute myeloid leukaemia due to polymorphisms in detoxification and DNA repair enzymes.
BACKGROUND
Polymorphisms in genes involved in detoxification and DNA-repair pathways may modify the individual's risk for genomic damage, and, as a consequence, the risk of developing malignant diseases.


METHODS
We performed a case-control study including 160 cases of acute myeloid leukaemia (AML) and 162 matched controls to test the impact of six genomic polymorphisms on the risk to develop AML and/or therapy-related AML.


RESULTS
We found a significantly higher prevalence of the polymorphic variants RAD51-G135C and CYP3A4-A-290G genes in AML cases, when compared with controls (P = 0.02 and P = 0.04), increasing the risk of AML 2.1-folds (95% CI: 1.1-4.0) and 3.2-fold (95% CI: 1.1-11.5), respectively. Carriers of both the RAD51-G135C and CYP3A4-A-290G variants were at highest AML risk (P = 0.003; OR:13,6; 95% CI: 2.0-585.5), suggesting a synergistic effect between these polymorphisms.


CONCLUSIONS
These results suggest that polymorphic variants in DNA-repair and detoxification enzymes may co-operate in modulating the individual's risk of AML.
Voso
M T
MT
Istituto di Ematologia, Universita' Cattolica del Sacro Cuore, Roma, Italy. mtvoso@rm.unicatt.it
Fabiani
E
E
D'Alo'
F
F
Guidi
F
F
Di Ruscio
A
A
Sica
S
S
Pagano
L
L
Greco
M
M
Hohaus
S
S
Leone
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000235:genetics; D008297:Male; D050216:Metabolic Detoxication, Phase I / Q000235:genetics*; D050217:Metabolic Detoxication, Phase II / Q000235:genetics*; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D011110:Polymorphism, Genetic; D051135:Rad51 Recombinase / Q000235:genetics; D012307:Risk Factors
D004268:DNA-Binding Proteins; D007527:Isoenzymes; C110901:X-ray repair cross complementing protein 3; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; D051135:Rad51 Recombinase; D045643:DNA Repair Enzymes