Single-nucleotide polymorphisms in reductase genes are not associated with response to daunorubicin-based remission induction.

BACKGROUND To improve the quality of care for patients with acute myeloid leukemia (AML), biomarkers predictive of response to the standard daunorubicin-based induction therapy are needed. Genetic variants affecting daunorubicin metabolism are attractive candidates for such biomarkers. METHODS We have previously shown that 13 of the naturally occurring nonsynonymous single-nucleotide polymorphisms (SNP) in the reductase genes affect daunorubicin metabolism in vitro. Here, we test these SNPs individually and jointly for association with response to one cycle of daunorubicin-based chemotherapy in a sample of 189 patients with acute myelogenous leukemia. RESULTS Of the 13 SNPs included in this study, only 5 passed quality control filters. No association was found between these 5 SNPs and response to one cycle of daunorubicin-based induction therapy in either individual or joint effect tests. CONCLUSIONS Despite their showing in vitro effect on metabolic rate of daunorubicin, the nonsynonymous SNPs in the reductase genes on their own are not significant contributors to the observed variability in response to daunorubicin therapy and thus, as singularities, are not useful biomarkers of this outcome. IMPACT The results of this investigation provide important information for studies on personalization of anthracycline-based therapies.