Article
No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival
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- (1) The Ohio State University, grid.261331.4
- (2) Roswell Park Cancer Institute, grid.240614.5
- (3) Mayo Clinic, grid.66875.3a
- (4) University of California, Irvine, grid.266093.8
- (5) Rutgers, The State University of New Jersey, grid.430387.b
- (6) Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
- (7) Duke University Hospital, grid.189509.c
- (8) Haukeland University Hospital, grid.412008.f
- (9) University of Bergen, grid.7914.b
- (10) Oregon Health & Science University, grid.5288.7
- (11) Cancer Genetics Laboratory, East Melbourne, Australia
- (12) University of Melbourne, grid.1008.9
- (13) QIMR Berghofer Medical Research Institute, grid.1049.c
- (14) Brigham and Women's Hospital, grid.62560.37
- (15) Harvard University, grid.38142.3c
- (16) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
- (17) New York University Langone Medical Center, grid.240324.3
- (18) University of Pittsburgh, grid.21925.3d
- (19) Hannover Medical School, grid.10423.34
- (20) Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
- (21) Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens Stiftung/Knappschaft GmbH, Essen, Germany
- (22) Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
- (23) University Hospital Southampton NHS Foundation Trust, grid.430506.4
- (24) University of Southampton, grid.5491.9
- (25) Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- (26) Cedars-Sinai Medical Center, grid.50956.3f
- (27) University College London, grid.83440.3b
- (28) Beatson West of Scotland Cancer Centre, grid.422301.6
- (29) Pomeranian Medical University, grid.107950.a
- (30) Department of Gynaecology, Rigshospitalet, University of Copenhagen, Herlev, Denmark
- (31) University of Copenhagen, grid.5254.6, KU
- (32) Danish Cancer Society, grid.417390.8
- (33) German Cancer Research Center, grid.7497.d
- (34) University Cancer Center Hamburg, grid.412315.0
- (35) Rzeszów University, grid.13856.39
- (36) KU Leuven, grid.5596.f
- (37) Department of Gynecology, The Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- (38) Stanford University, grid.168010.e
- (39) University of Glasgow, grid.8756.c
- (40) University of Pittsburgh Cancer Institute, grid.478063.e
- (41) The University of Texas Health Science Center at Houston, grid.267308.8
- (42) University of Michigan, grid.214458.e
- (43) University of Southern California, grid.42505.36
- (44) University of Cambridge, grid.5335.0
- (45) Garvan Institute of Medical Research, grid.415306.5
- (46) UNSW Sydney, grid.1005.4
- (47) Fred Hutchinson Cancer Research Center, grid.270240.3
- (48) University of Washington, grid.34477.33
- (49) University of Virginia, grid.27755.32
- (50) University Medical Center Hamburg-Eppendorf, grid.13648.38
- (51) Praxis für Humangenetik, grid.461735.2
- (52) Glasgow Royal Infirmary, grid.411714.6
- (53) Icahn School of Medicine at Mount Sinai, grid.59734.3c
- (54) Universitair Ziekenhuis Leuven, grid.410569.f
- (55) National Cancer Institute, grid.48336.3a
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Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses.Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival.Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing (P < 3.5 × 10-5), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival.Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes.Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420-4. ©2016 AACR.
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