No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival
Year: 2016
Type: article
Study design: Observational Study
Abstract: 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.
Authors: Lara E. Sucheston-Campbell, Rikki Cannioto, Alyssa I. Clay, John Lewis Etter, Kevin H. Eng, Song Liu, Sebastiano Battaglia, Qiang Hu, J. Brian Szender, Albina Minlikeeva, Janine M. Joseph, Paul Mayor, Scott I. Abrams, Brahm H. Segal, Paul K. Wallace, Kah Teong Soh, Emese Zsiros, Hoda Anton-Culver, Elisa V. Bandera, Matthias W. Beckmann, Andrew Berchuck, Line Bjorge, Amanda Bruegl, Ian G. Campbell, Shawn Patrice Campbell, Georgia Chenevix-Trench, Daniel W. Cramer, Agnieszka Dansonka-Mieszkowska, Fanny Dao, Brenda Diergaarde, Thilo Doerk, Jennifer A. Doherty, Andreas du Bois, Diana Eccles, Svend Aage Engelholm, Peter A. Fasching, Simon A. Gayther, Aleksandra Gentry-Maharaj, Rosalind M. Glasspool, Marc T. Goodman, Jacek Gronwald, Philipp Harter, Alexander Hein, Florian Heitz, Peter Hillemmanns, Claus Høgdall, Estrid V.S. Høgdall, Tomasz Huzarski, Allan Jensen, Sharon E. Johnatty, Audrey Jung, Beth Y. Karlan, Reudiger Klapdor, Tomasz Kluz, Bożena Konopka, Susanne Krüger Kjær, Jolanta Kupryjanczyk, Diether Lambrechts, Jenny Lester, Jan Lubiński, Douglas A. Levine, Lene Lundvall, Valerie McGuire, Iain A. McNeish, Usha Menon, Francesmary Modugno, Roberta B. Ness, Sandra Orsulic, James Paul, Celeste Leigh Pearce, Tanja Pejovic, Paul Pharoah, Susan J. Ramus, Joseph Rothstein, Mary Anne Rossing, Matthias Rübner, Joellen M. Schildkraut, Barbara Schmalfeldt, Ira Schwaab, Nadeem Siddiqui, Weiva Sieh, Piotr Sobiczewski, Honglin Song, Kathryn L. Terry, Els Van Nieuwenhuysen, Adriaan Vanderstichele, Ignace Vergote, Christine S. Walsh, Penelope M. Webb, Nicolas Wentzensen, Alice S. Whittemore, Anna H. Wu, Argyrios Ziogas, Kunle Odunsi, Jenny Chang-Claude, Ellen L. Goode, Kirsten B. Moysich
Institutions: The Ohio State University, Roswell Park Comprehensive Cancer Center, Mayo Clinic, University of California, Irvine, Rutgers Cancer Institute, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen, Duke University, Duke Medical Center, Haukeland University Hospital, University of Bergen, Oregon Health & Science University, The University of Melbourne, QIMR Berghofer Medical Research Institute, Brigham and Women's Hospital, Harvard University, The Maria Sklodowska-Curie National Research Institute of Oncology, NYU Langone Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, New York University, University of Pittsburgh, Medizinische Hochschule Hannover, Dartmouth College, Helios Dr. Horst Schmidt Kliniken Wiesbaden, Kliniken Essen-Mitte, University Hospital Southampton NHS Foundation Trust, University of Southampton, University of Copenhagen, Rigshospitalet, Cedars-Sinai Medical Center, University College London, Beatson West of Scotland Cancer Centre, International Hereditary Cancer Center, Pomeranian Medical University, Herlev Hospital, Danish Cancer Society, Universität Hamburg, German Cancer Research Center, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, University of Rzeszów, KU Leuven, Stanford Medicine, Stanford University, Cancer Research UK Scotland Institute, University of Glasgow, Magee-Womens Research Institute, UPMC Hillman Cancer Center, The University of Texas Health Science Center at Houston, University of Southern California, University of Michigan, University of Cambridge, Garvan Institute of Medical Research, UNSW Sydney, The Kinghorn Cancer Centre, University of Washington, Fred Hutch Cancer Center, University of Virginia, Bundeskriminalamt, Glasgow Royal Infirmary, Icahn School of Medicine at Mount Sinai, Universitair Ziekenhuis Leuven, National Cancer Institute, Division of Cancer Epidemiology and Genetics
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: SURVEILLANCE EPIDEMIOLOGY &END RESULTS PROGRAM, UNRESOLVED PUBLIC HEALTH ISSUES RELATED TO HT AND CANCER, G1132776228, G1478067267, G1791794685, G1885355073, SURVEILLANCE EPIDEMIOLOGY AND END RESULTS, G204658482, G2066431456, G213336435, Steroid Hormone Genes and Ovarian Cancer Risk, G215985982, Ovarian Cancer and Gonadotropin Signaling, G2307404120, Northern California Cooperative Family Registry for Breast Cancer, G2449870768, G2519210884, Obesity in ovarian cancer prognosis, G2838565599, G2899816875, Hereditary Breast Cancer: Genetic and Molecular Studies, G3120360579, The Molecular Epidemiology Of Ovarian Cancer, UCLA Clinical and Translational Science Institute, G328081645, G3307645897, General Clinical Research Center, G3695342494, G4162991602, G4887430338, Dana-Farber/Harvard Cancer Center Ovarian Cancer SPORE, Collaborative Genetic Study of Ovarian Cancer Risk, Epidemiology of Ovarian Cancer:New Hypotheses, Genetic Epidemiology of Ovarian and Prostate Cancer, G6283257732, G6433449787, Inflammation and Ovarian Cancer, G7378152860, Genetic Variation in the NF-kappaB Pathway and Ovarian Cancer Etiology, Interdisciplinary Training in Cancer Epidemiology at UB, G8319404918, G835684289, Cellular and Molecular Medicine, Novel immunological biomarkers ovarian cancer prognosis, Cancer Center Support Grant, Mayo Clinic Comprehensive Cancer Center Support Grant, Roswell Park Ovarian Cancer SPORE, Roswell Park Cancer Center Support Grant, University of Southern California Norris Comprehensive Cancer Center Support Grant (CCSG), G921773184
OpenAlex ID: W2525188489