Carboplatin/taxane-induced gastrointestinal toxicity: A pharmacogenomics study on the SCOTROC1 trial

Y. J. He, S. J. Winham, J. M. Hoskins, S. Glass, J. Paul, R. Brown, A. Motsinger-Reif, H. L. McLeod

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P<0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients.

Original languageEnglish (US)
Pages (from-to)243-248
Number of pages6
JournalPharmacogenomics Journal
Volume16
Issue number3
DOIs
StatePublished - Jun 1 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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    He, Y. J., Winham, S. J., Hoskins, J. M., Glass, S., Paul, J., Brown, R., Motsinger-Reif, A., & McLeod, H. L. (2016). Carboplatin/taxane-induced gastrointestinal toxicity: A pharmacogenomics study on the SCOTROC1 trial. Pharmacogenomics Journal, 16(3), 243-248. https://doi.org/10.1038/tpj.2015.52