TY  - JOUR
A1  - Fasching, Peter Andreas
A1  - Häberle, Lothar
A1  - Rack, Brigitte
A1  - Li, Liang
A1  - Hein, Alexander
A1  - Ekici, Arif Bülent
A1  - Reis, Andre
A1  - Lux, Michael Patrick
A1  - Cunningham, Julie M.
A1  - Rübner, Matthias
A1  - Jenkins, Gergory
A1  - Fridley, Brooke
A1  - Schneeweiss, Andreas
A1  - Tesch, Hans
A1  - Lichtenegger, Werner
A1  - Fehm, Tanja
A1  - Heinrich, Georg
A1  - Rezai, Mahdi
A1  - Beckmann, Matthias Wilhelm
A1  - Janni, Wolfgang
A1  - Weinshilboum, Richard M.
A1  - Wang, Liewei
T1  - Clinical validation of genetic variants associated with in vitro chemotherapy-related lymphoblastoid cell toxicity
T2  - OncoTarget
N2  - 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.
KW  - chemotherapy
KW  - neutropenia
KW  - leukopenia
KW  - SNP
KW  - polymorphism
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44193
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-441934
SN  - 1949-2553
N1  - All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
VL  - 8
SP  - 1
EP  - 11
PB  - Impact Journals LLC
CY  - [s. l.]
ER  -