ABCB1 (MDR1)rs1045642 is associated with increased overall survival in plasma cell myeloma

Authors:
  • MCMark A. Catherwood
    Mark A. Catherwood
  • NONick Orr
    Nick Orr
  • LGLeeona Galligan
    Leeona Galligan
  • CHClare Hodkinson
    Clare Hodkinson
  • MDMary B. Drake
    Mary B. Drake
  • PKPaul J. Kettle
    Paul J. Kettle
  • TMT. C. M. “Curly” Morris
    T. C. M. “Curly” Morris
  • HAH. Denis Alexander
    H. Denis Alexander
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Abstract
Multi-drug resistance (MDR) may compromise the successful management of haematological malignancies, impairing the effectiveness of chemotherapy. The P-glycoprotein (P-gp) drug efflux pump, encoded by the gene ABCB1 (MDR1), is the most widely studied component in MDR. A single nucleotide polymorphism (SNP) has been identified within ABCB1, rs1045642 (C3435T), which may alter P-gp substrate specificity and have an impact on the effectiveness of treatment, and hence overall survival (OS). We estimated the frequency of this SNP in the Northern Irish population and investigated its impact on the OS of patients with plasma cell myeloma (PCM). There was no significant difference in the frequency of rs1045642 between the PCM cohort and an age- and gender-matched control population. Findings within the PCM cohort suggest that rs1045642 genotype influences OS (p = 2 x 10(-2)). If confirmed in larger studies, these results suggest that genotyping rs1045642 may be a useful predictor of outcome in PCM and could indicate modified treatment modalities in certain individuals.

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