Genetic markers associated with platinum/taxanes induced gastrointestinal toxicity in SCOTROC1 trial

He, Y., Wood, S.J., Paul, J. , Motsinger-Reif, A., Auman, T., Hoskins, J.M., Brown, R. and McLeod, H.L. (2011) Genetic markers associated with platinum/taxanes induced gastrointestinal toxicity in SCOTROC1 trial. Clinical Pharmacology and Therapeutics, 89, S4-S5. (doi:10.1038/clpt.2010.326)

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Publisher's URL: http://dx.doi.org/10.1038/clpt.2010.326

Abstract

<b>BACKGROUND</b>: Platinum/taxane is first line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, and even death because of chemotherapy induced gastrointestinal (GI) toxicity.<p></p> <b>METHODS</b>: A candidate gene association study was conducted to assess 1569 single nucleotide polymorphisms (SNP) from 58 genes in 808 patients who received platinum/taxane in Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into two cohorts consisting of 404 patients. Clinical covariates and genetic variants associated with grade 3-4 GI toxicity and overall survival in the first discovery cohort were evaluated in the second replication cohort.<p></p> <b>RESULTS</b>: Survival status, treatment arm, grade 2 sensory neuropathy, CA125 response, and Eastern Cooperative Oncology Group performance status were associated with GI toxicity. Patients with risk genotypes for seven SNPs of <i>ATP7B, GSR, VEGF</i> and <i>SCN10A</i> genes were at 1.7 to 18.0 times higher risk of developing platinum/taxane-induced GI toxicity than patients with non-risk genotypes (P<0.01). Patients with the rs9369421 GG genotype have a hazard rate 0.0000303% than that of patients with AA genotype (P=0.02).<p></p> <b>CONCLUSION</b>: Seven SNPs increased the risk of developing platinum/taxane-induced GI toxicity. Patients with rs9369421 GG genotype had an improved survival compared with AA genotype. Our data suggest new genetic markers for predicting platinum/taxane toxicity and prognosis in ovarian cancer patients.<p></p>

Item Type:Articles
Additional Information:Paper presented at the 2011 Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, Dallas, TX USA, 2-5 Mar 2011.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Paul, Mr James
Authors: He, Y., Wood, S.J., Paul, J., Motsinger-Reif, A., Auman, T., Hoskins, J.M., Brown, R., and McLeod, H.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Clinical Pharmacology and Therapeutics
Publisher:Nature Publishing Group
ISSN:0009-9236
ISSN (Online):1532-6535

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