Bidadi B, Liu D, Kalari KR, Rübner M, Hein A, Beckmann M, Rack B, Janni W, Fasching P, Weinshilboum RM, Wang L (2018)
Publication Type: Journal article
Publication year: 2018
Book Volume: 9
Pages Range: 158
Neutropenia secondary to chemotherapy in breast cancer patients can be life-threatening and there are no biomarkers available to predict the risk of drug-induced neutropenia in those patients. We previously performed a genome-wide association study (GWAS) for neutropenia events in women with breast cancer who were treated with 5-fluorouracil, epirubicin and cyclophosphamide and recruited to the SUCCESS-A trial. A genome-wide significant single-nucleotide polymorphism (SNP) signal in the tumor necrosis factor superfamily member 13B () gene, encoding the cytokine B-cell activating factor (BAFF), was identified in that GWAS. Taking advantage of these existing GWAS data, in the present study we utilized a pathway-based analysis approach by leveraging knowledge of the pharmacokinetics and pharmacodynamics of drugs and breast cancer pathophysiology to identify additional SNPs/genes associated with the underlying etiology of chemotherapy-induced neutropenia. We identified three SNPs in the hyaluronan mediated motility receptor ( gene that were significantly associated with neutropenia ( < 1.0E-04). Those three SNPs were trans-expression quantitative trait loci for the expression of ( < 1.0E-04). The minor allele of these SNPs was associated with a decreased mRNA level. Additional functional studies performed with lymphoblastoid cell lines (LCLs) demonstrated that LCLs possessing the minor allele for the SNPs were more sensitive to drug treatment. Knock-down of in LCLs and HL-60 promyelocytic cells and treatment of those cells with BAFF modulated the cell sensitivity to chemotherapy treatment. These results demonstrate that SNP-dependent cytotoxicity of these chemotherapeutic agents might be related to expression level. In summary, utilizing a pathway-based approach for the analysis of GWAS data, we identified additional SNPs in the gene that were associated with neutropenia and also were correlated with expression.
APA:
Bidadi, B., Liu, D., Kalari, K.R., Rübner, M., Hein, A., Beckmann, M.,... Wang, L. (2018). Pathway-Based Analysis of Genome-Wide Association Data Identified SNPs in as Biomarker for Chemotherapy- Induced Neutropenia in Breast Cancer Patients. Frontiers in Pharmacology, 9, 158. https://doi.org/10.3389/fphar.2018.00158
MLA:
Bidadi, Behzad, et al. "Pathway-Based Analysis of Genome-Wide Association Data Identified SNPs in as Biomarker for Chemotherapy- Induced Neutropenia in Breast Cancer Patients." Frontiers in Pharmacology 9 (2018): 158.
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