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Madden, Ebony

https://orcid.org/0000-0003-4510-9563

Mayo Clinic

National Human Genome Research Institute

Citations 1

Identification of Two Genetic Loci Associated with Leukopenia after Chemotherapy in Patients with Breast Cancer
Fasching, Peter A. , Liu, Duan , Scully, Steve, Ingle, James N. , Lyra, Paulo C. , Rack, Brigitte , Hein, Alexander , Ekici, Arif B. , Reis, André , Schneeweiß, Andreas , Tesch, Hans , Heinrich, Georg, Beckmann, Matthias W. , Ruebner, Matthias , Huebner, Hanna , Lambrechts, Diether , Madden, Ebony , Shen, Jess, Romm, Jane, Doheny, Kim, Jenkins, Gregory D. , Cunningham, Julie M. , Janni, Wolfgang , Schaid, Daniel J. , Häberle, Lothar , Weinshilboum, Richard M. , Wang, Liewei , Lambrechts, Diether , Lambrechts, Diether , Li, Liang , Fridley, Brooke L , Cunningham, Julie M , Janni, Wolfgang , Monteiro, Alvaro N , Ingle, J , Lambrechts, Diether , Hein, Alexander , Ekici, Arif B , Reis, André , Morais Lyra, Paulo Cilas , Liu, Duan , Fehm, Tanja , Carlson, Erin E. , Li, Liang , Fridley, Brooke L. , Monteiro, Álvaro N.A. , Weinshilboum, Richard M.

Clinical Cancer Research | June 27, 2022 | Volume: 28 | Issue: 15 | Pages: 3342-3355

10.1158/1078-0432.ccr-20-4774 Get It

Abstract Purpose: To identify molecular predictors of grade 3/4 neutropenic or leukopenic events (NLE) after chemotherapy using a genome-wide association study (GWAS). Experimental Design: A GWAS was performed on patients in the phase III chemotherapy study SUCCESS-A (n = 3,322). Genotyping was done using the Illumina HumanOmniExpress-12v1 array. Findings were functionally validated with cell culture models and the genotypes and gene expression of possible causative genes were correlated with clinical treatment response and prognostic outcomes. Results: One locus on chromosome 16 (rs4784750; NLRC5; P = 1.56E-8) and another locus on chromosome 13 (rs16972207; TNFSF13B; P = 3.42E-8) were identified at a genome-wide significance level. Functional validation revealed that expression of these two genes is altered by genotype-dependent and chemotherapy-dependent activity of two transcription factors. Genotypes also showed an association with disease-free survival in patients with an NLE. Conclusions: Two loci in NLRC5 and TNFSF13B are associated with NLEs. The involvement of the MHC I regulator NLRC5 implies the possible involvement of immuno-oncological pathways.