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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, Andre; Schneeweiss, Andreas; Tesch, Hans; Fehm, Tanja N; Heinrich, Georg; Beckmann, Matthias W; Ruebner, Matthias; Huebner, Hanna; Lambrechts, Diether; Madden, Ebony; Shen, Jess; Romm, Jane; Doheny, Kim; Jenkins, Gregory D; Carlson, Erin E; Li, Liang; Fridley, Brooke L; Cunningham, Julie M; Janni, Wolfgang; Monteiro, Alvaro N A; Schaid, Daniel J; Häberle, Lothar; Weinshilboum, Richard M; Wang, Liewei.
Afiliação
  • Fasching PA; Department of Gynecology and Obstetrics, University Breast Center for Franconia, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nürnberg, Comprehensive Cancer Center Erlangen EMN, Erlangen, Germany.
  • Liu D; Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.
  • Scully S; Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.
  • Ingle JN; Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
  • Lyra PC; Biotechnology/RENORBIO Program, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil.
  • Rack B; Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany.
  • Hein A; Department of Gynecology and Obstetrics, University Breast Center for Franconia, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nürnberg, Comprehensive Cancer Center Erlangen EMN, Erlangen, Germany.
  • Ekici AB; Institute of Human Genetics, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Reis A; Institute of Human Genetics, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Schneeweiss A; National Center for Tumor Diseases, Division of Gynecologic Oncology, Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany.
  • Tesch H; Onkologie Bethanien, Frankfurt am Main, Germany.
  • Fehm TN; Department of Gynecology and Obstetrics, Düsseldorf University Hospital, Heinrich Heine University, Düsseldorf, Germany.
  • Heinrich G; Schwerpunktpraxis für Gynäkologische Onkologie, Fürstenwalde, Germany.
  • Beckmann MW; Department of Gynecology and Obstetrics, University Breast Center for Franconia, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nürnberg, Comprehensive Cancer Center Erlangen EMN, Erlangen, Germany.
  • Ruebner M; Department of Gynecology and Obstetrics, University Breast Center for Franconia, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nürnberg, Comprehensive Cancer Center Erlangen EMN, Erlangen, Germany.
  • Huebner H; Department of Gynecology and Obstetrics, University Breast Center for Franconia, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nürnberg, Comprehensive Cancer Center Erlangen EMN, Erlangen, Germany.
  • Lambrechts D; VIB Center for Cancer Biology, VIB and Laboratory for Translational Genetics, KU Leuven, Leuven, Belgium.
  • Madden E; Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, Maryland.
  • Shen J; Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
  • Romm J; McKusick-Nathans Department of Genetic Medicine, Center for Inherited Disease Research, Johns Hopkins University, Baltimore, Maryland.
  • Doheny K; McKusick-Nathans Department of Genetic Medicine, Center for Inherited Disease Research, Johns Hopkins University, Baltimore, Maryland.
  • Jenkins GD; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
  • Carlson EE; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
  • Li L; Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.
  • Fridley BL; Department of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tiantan Xili, Beijing, China.
  • Cunningham JM; Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.
  • Janni W; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
  • Monteiro ANA; Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany.
  • Schaid DJ; Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
  • Häberle L; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
  • Weinshilboum RM; Department of Gynecology and Obstetrics, University Breast Center for Franconia, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nürnberg, Comprehensive Cancer Center Erlangen EMN, Erlangen, Germany.
  • Wang L; Department of Gynecology and Obstetrics, Unit of Biostatistics, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Clin Cancer Res ; 28(15): 3342-3355, 2022 08 02.
Article em En | MEDLINE | ID: mdl-35653140
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Leucopenia Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Clin Cancer Res Assunto da revista: NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Alemanha
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Leucopenia Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Clin Cancer Res Assunto da revista: NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Alemanha