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. Patients and 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.