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Silent polymorphisms speak: how they affect pharmacogenomics and the treatment of cancer

Zuben E Sauna1, Chava Kimchi-Sarfaty, Suresh V Ambudkar

  • 1Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH and Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.

Cancer Research
|October 19, 2007
PubMed

Insights

Genetic variations, including synonymous single-nucleotide polymorphisms (SNPs), significantly impact drug response and cancer therapy. Our research indicates these "silent" SNPs in ABCB1 can alter protein function, highlighting their underappreciated role in personalized medicine.

Area of Science:

  • Genetics
  • Pharmacology
  • Oncology

Background:

  • Human genome polymorphisms cause varied drug responses by altering pharmacokinetics or cellular drug effects.
  • Pharmacogenomics aims to personalize medical treatment using an individual's genetic makeup.
  • Synonymous single-nucleotide polymorphisms (SNPs) are often ignored in pharmacogenomic studies, presumed to be functionally silent.

Purpose of the Study:

  • To investigate the functional impact of synonymous SNPs in the ABCB1 gene.
  • To highlight the significance of synonymous polymorphisms in drug metabolizing enzymes and transporters for anticancer therapy.

Main Methods:

  • Analysis of synonymous single-nucleotide polymorphisms (SNPs) in the ABCB1 gene.
  • Assessment of the effect of these SNPs on P-glycoprotein conformation and function.

Main Results:

  • Synonymous SNPs in ABCB1 were shown to affect protein conformation and function.
  • This challenges the assumption that synonymous SNPs are functionally silent.

Conclusions:

  • Synonymous polymorphisms may play a more substantial role in pharmacogenomics and anticancer therapy than previously recognized.
  • Personalized medicine strategies should consider the impact of synonymous SNPs on drug efficacy and resistance.

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