Clinical validation of genetic variants associated with in vitro chemotherapy-related lymphoblastoid cell toxicity

Fasching P, Häberle L, Rack B, Li L, Hein A, Ekici AB, Reis A, Lux MP, Cunningham JM, Rübner M, Jenkins G, Fridley B, Schneeweiss A, Tesch H, Lichtenegger W, Fehm T, Heinrich G, Rezai M, Beckmann M, Janni W, Weinshilboum RM, Wang L (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Oncotarget Impact Journals

Book Volume: 8

Pages Range: 78133-78143

Journal Issue: 44

DOI: 10.18632/oncotarget.17726

Abstract

Hematotoxicity is one of the major side effects of chemotherapy. The aim of this study was to examine the association between single nucleotide polymorphisms (SNPs) and hematotoxicity in breast cancer patients in a subset of patients of the SUCCESS prospective phase III chemotherapy study. All patients (n = 1678) received three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by three cycles of docetaxel or docetaxel/gemcitabine, depending on randomization. Germline DNA was genotyped for 246 SNPs selected from a previous genome-wide association study (GWAS) in a panel of lymphoblastoid cell lines, with gemcitabine toxicity as the phenotype. All SNPs were tested for their value in predicting grade 3 or 4 neutropenic or leukopenic events (NLEs). Their prognostic value in relation to overall survival and disease-free survival was also tested. None of the SNPs was found to be predictive for NLEs during treatment with docetaxel/gemcitabine. Two SNPs in and close to the PIGB gene significantly improved the prediction of NLEs after FEC, in addition to the factors of age and body surface area. The top SNP (rs12050587) had an odds ratio of 1.38 per minor allele (95% confidence interval, 1.17 to 1.62). No associations were identified for predicting disease-free or overall survival. Genetic variance in the PIGB gene may play a role in determining interindividual differences in relation to hematotoxicity after FEC chemotherapy.

Authors with CRIS profile

Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe Alexander Hein Department of Obstetrics and Gynaecology Arif Bülent Ekici Institute of Human Genetics André Wiesmann da Silva Reis Lehrstuhl für Humangenetik Matthias Rübner Department of Obstetrics and Gynaecology Matthias Beckmann Lehrstuhl für Geburtshilfe und Frauenheilkunde

Involved external institutions

Mayo Clinic US United States (USA) (US) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) Luisenkrankenhaus Düsseldorf DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Heinrich-Heine-Universität Düsseldorf DE Germany (DE) Centrum für Hämatologie und Onkologie Bethanien DE Germany (DE)

How to cite

APA:

Fasching, P., Häberle, L., Rack, B., Li, L., Hein, A., Ekici, A.B.,... Wang, L. (2017). Clinical validation of genetic variants associated with in vitro chemotherapy-related lymphoblastoid cell toxicity. Oncotarget, 8(44), 78133-78143. https://doi.org/10.18632/oncotarget.17726

MLA:

Fasching, Peter, et al. "Clinical validation of genetic variants associated with in vitro chemotherapy-related lymphoblastoid cell toxicity." Oncotarget 8.44 (2017): 78133-78143.

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