Increased risk of acute myeloid leukaemia due to polymorphisms in detoxification and DNA repair enzymes.

Francesco D'Alo', Livio Pagano, Simona Sica, Stefan Hohaus, Maria Teresa Voso, Emiliano Fabiani, Francesco Guidi, Annalisa Di Ruscio, Mariangela Greco

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1523-1528
Number of pages6
JournalAnnals of Oncology
Publication statusPublished - 2007

Keywords

  • AML
  • Polymorphism

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