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Genetic factors underlying the risk of bortezomib induced peripheral neuropathy in multiple myeloma patients

Sophie L Corthals1, Rowan Kuiper, David C Johnson

  • 1Erasmus Medical Center, Rotterdam, The Netherlands.

Haematologica
|July 28, 2011
PubMed

Insights

Genetic factors for bortezomib induced peripheral neuropathy in multiple myeloma patients were investigated. No significant associations were found after correction, but pathway analysis suggested links to neurological disease.

Area of Science:

  • Pharmacogenetics
  • Oncology
  • Neurology

Background:

  • Bortezomib induced peripheral neuropathy is a significant dose-limiting side effect in multiple myeloma treatment.
  • Identifying genetic risk factors is crucial for managing this adverse event.

Purpose of the Study:

  • To identify genetic risk factors for bortezomib induced peripheral neuropathy in multiple myeloma patients.
  • To explore the pharmacogenetic basis of this common side effect.

Main Methods:

  • A pharmacogenetic association study was conducted using discovery (n=238) and validation (n=231) datasets.
  • 2,149 single nucleotide polymorphisms were tested for association with bortezomib induced peripheral neuropathy.
  • Pathway analysis was performed on associated single nucleotide polymorphisms.

Main Results:

  • No single nucleotide polymorphisms showed significant association after multiplicity correction.
  • 56 single nucleotide polymorphisms demonstrated uncorrected association, with pathway analysis implicating neurological disease.
  • rs619824 in CYP17A1 showed pointwise significance in the validation set.

Conclusions:

  • While no definitive genetic markers were identified after stringent correction, preliminary findings suggest potential involvement of neurological pathways.
  • Further research is warranted to elucidate the genetic underpinnings of bortezomib induced peripheral neuropathy.

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