The effect of rs5758550 on CYP2D6*2 phenotype and formation of endoxifen in breast cancer patients using tamoxifen

Pharmacogenomics. 2017 Aug;18(12):1125-1132. doi: 10.2217/pgs-2017-0080. Epub 2017 Jul 26.

Abstract

Aim: CYP2D6*2 is considered fully active, but it has been suggested that it only happens in the presence of rs5758550. This study aims to elucidate the impact of this enhancer.

Materials & methods: DNA and blood samples from women enrolled in the CYPTAM study (NTR1509) were analyzed. Fourteen CYP2D6*2 carriers without the enhancer were reclassified. The relationship of CYP2D6 phenotypes and drug levels was studied.

Results: After correction for the absence of the enhancer, the correlation between CYP2D6 phenotypes and endoxifen did not improve (R2: 0.290 vs 0.279). No difference was observed in mean concentrations between CYP2D6*2 individuals with and without the enhancer.

Conclusion: The rs5758550 enhancer does not lead to improved prediction of endoxifen levels in breast cancer patients.

Keywords: CYP2D6*2; endoxifen; enhancer; rs5758550; tamoxifen.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Cytochrome P-450 CYP2D6 / genetics*
  • Female
  • Genotype
  • Humans
  • Middle Aged
  • Phenotype
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / therapeutic use*
  • Young Adult

Substances

  • Antineoplastic Agents, Hormonal
  • Tamoxifen
  • 4-hydroxy-N-desmethyltamoxifen
  • Cytochrome P-450 CYP2D6