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

He, Y.J., Winham, S.J., Hoskins, J.M., Glass, S., Paul, J. , Brown, R., Motsinger-Reif, A. and McLeod, H.L. (2016) Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial. Pharmacogenomics Journal, 16(3), pp. 243-248. (doi: 10.1038/tpj.2015.52) (PMID:26194361)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Paul, Mr James
• Authors: He, Y.J., Winham, S.J., Hoskins, J.M., Glass, S., Paul, J., Brown, R., Motsinger-Reif, A., and McLeod, H.L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Pharmacogenomics Journal
• Publisher: Nature Publishing Group
• ISSN: 1470-269X
• ISSN (Online): 1473-1150
• Published Online: 21 July 2015
• Copyright Holders: Copyright © 2016 Macmillan Publishers Limited
• First Published: First pubilshed in Pharmacogenomics Journal 16(3): 243-248
• Publisher Policy: Reproduced in accordance with the publisher copyright policy