No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival.
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.
College of Pharmacy, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio.
Lara E
LE
Sucheston-Campbell
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
Rikki
R
Cannioto
Cancer Genetic Epidemiology, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
Alyssa I
AI
Clay
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
John Lewis
JL
Etter
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York.
Kevin H
KH
Eng
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York.
Song
S
Liu
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York.
Sebastiano
S
Battaglia
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York.
Qiang
Q
Hu
Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York.
J Brian
JB
Szender
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
Albina
A
Minlikeeva
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
Janine M
JM
Joseph
Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York.
Paul
P
Mayor
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York.
Scott I
SI
Abrams
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York.|Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York.
Brahm H
BH
Segal
Department of Flow & Image Cytometry, Roswell Park Cancer Institute, Buffalo, New York.
Paul K
PK
Wallace
Department of Flow & Image Cytometry, Roswell Park Cancer Institute, Buffalo, New York.
Kah Teong
KT
Soh
Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York.
Emese
E
Zsiros
Genetic Epidemiology Research Institute, School of Medicine, University of California Irvine, Irvine, California.
Hoda
H
Anton-Culver
Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
Elisa V
EV
Bandera
Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Matthias W
MW
Beckmann
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina.
Andrew
A
Berchuck
Department of Gynecology and Obstetrics, Haukeland University Horpital, Bergen, Norway.|Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway.
Line
L
Bjorge
Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon.
Amanda
A
Bruegl
Cancer Genetics Laboratory, East Melbourne, Australia.|Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
Ian G
IG
Campbell
Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon.
Shawn Patrice
SP
Campbell
Georgia
G
Chenevix-Trench
Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, Massachusetts.|Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Daniel W
DW
Cramer
Department of Pathology and Laboratory Diagnostics, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Agnieszka
A
Dansonka-Mieszkowska
Gynecologic Oncology, Laura and Isaac Pearlmutter Cancer Center, NYU Langone Medical Center, New York, New York.
Fanny
F
Dao
Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
Brenda
B
Diergaarde
Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Niedersachsen, Germany.
Thilo
T
Doerk
Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
Jennifer A
JA
Doherty
Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany.|Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany.
Andreas
A
du Bois
Faculty of Medicine, University of Southampton, Southampton, United Kingdom.|Wessex Clinical Genetics Service, Southampton University Hospitals Trust, Southampton, United Kingdom.
Diana
D
Eccles
Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Svend Aage
SA
Engelholm
Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Peter A
PA
Fasching
Center for Cancer Prevention and Translational Genomics, Cedars-Sinai Medical Center, Los Angeles, California.|Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.
Simon A
SA
Gayther
Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
Aleksandra
A
Gentry-Maharaj
The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
Rosalind M
RM
Glasspool
Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.|Department of Biomedical Sciences, Community and Population Health Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Marc T
MT
Goodman
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
Jacek
J
Gronwald
Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany.
Philipp
P
Harter
Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Alexander
A
Hein
Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany.|Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany.
Florian
F
Heitz
Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Niedersachsen, Germany.
Peter
P
Hillemmanns
Department of Gynaecology, Rigshospitalet, University of Copenhagen, Herlev, Denmark.
Claus
C
Høgdall
Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.|Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
Estrid V S
EV
Høgdall
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
Tomasz
T
Huzarski
Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
Allan
A
Jensen
Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, Herston, Australia.
Sharon E
SE
Johnatty
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.|University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Heidelberg, Germany.
Audrey
A
Jung
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Beth Y
BY
Karlan
Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Niedersachsen, Germany.
Reudiger
R
Klapdor
Clinic of Obstetrics and Gynecology, Institute of Midwifery and Emergency Medicine, Faculty of Medicine, University of Rzeszów, Rzeszów, Poland.
Tomasz
T
Kluz
Department of Pathology and Laboratory Diagnostics, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Bożena
B
Konopka
Department of Gynaecology, Rigshospitalet, University of Copenhagen, Herlev, Denmark.|Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
Susanne Krüger
SK
Kjær
Department of Pathology and Laboratory Diagnostics, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Jolanta
J
Kupryjanczyk
Department of Oncology, Laboratory for Translational Genetics, Vesalius Research Center, University of Leuven, Leuven, Belgium.
Diether
D
Lambrechts
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Jenny
J
Lester
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
Jan
J
Lubiński
Gynecologic Oncology, Laura and Isaac Pearlmutter Cancer Center, NYU Langone Medical Center, New York, New York.
Douglas A
DA
Levine
Department of Gynecology, The Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Lene
L
Lundvall
Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, California.
Valerie
V
McGuire
Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow, United Kingdom.
Iain A
IA
McNeish
Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
Usha
U
Menon
Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.|Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.|Ovarian Cancer Center of Excellence, Womens Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
Francesmary
F
Modugno
The University of Texas School of Public Health, Houston, Texas.
Roberta B
RB
Ness
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Sandra
S
Orsulic
The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
James
J
Paul
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan.|Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
Celeste Leigh
CL
Pearce
Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon.|Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
Tanja
T
Pejovic
Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.|Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
Paul
P
Pharoah
School of Women's and Children's Health, University of New South Wales, New South Wales, Australia.|The Kinghorn Cancer Centre, Garvan Institute of Medical Research, New South Wales, New South Wales, Australia.
Susan J
SJ
Ramus
Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, California.
Joseph
J
Rothstein
Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Department of Epidemiology, University of Washington, Seattle, Washington.
Mary Anne
MA
Rossing
Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Matthias
M
Rübner
Department of Public Health Sciences, The University of Virginia, Charlottesville, Virginia.
Joellen M
JM
Schildkraut
Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Barbara
B
Schmalfeldt
Praxis für Humangenetik, Wiesbaden, Germany.
Ira
I
Schwaab
Department of Gynaecological Oncology, Glasgow Royal Infirmary, Glasgow, United Kingdom.
Nadeem
N
Siddiqui
Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.|Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Weiva
W
Sieh
Department of Gynecologic Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Piotr
P
Sobiczewski
Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
Honglin
H
Song
Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, Massachusetts.|Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Kathryn L
KL
Terry
Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
Els
E
Van Nieuwenhuysen
Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
Adriaan
A
Vanderstichele
Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
Ignace
I
Vergote
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Christine S
CS
Walsh
Population Health Department, QIMR Berghofer Medical Research Institute, Herston, Australia.
Penelope M
PM
Webb
Division of Cancer Epidemiology and Genetics, NCI, Bethesda, Maryland.
Nicolas
N
Wentzensen
Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, California.
Alice S
AS
Whittemore
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
Anna H
AH
Wu
Department of Epidemiology, University of California Irvine, Irvine, California.
Argyrios
A
Ziogas
Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York.
Kunle
K
Odunsi
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.|University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Heidelberg, Germany.
Jenny
J
Chang-Claude
Department of Health Science Research, Mayo Clinic, Rochester, Minnesota.
Ellen L
EL
Goode
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York. kirsten.moysich@roswellpark.org.
Kirsten B
KB
Moysich
D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006801:Humans; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000276:immunology / Q000401:mortality*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000276:immunology / Q000401:mortality*
Cancer Immunol Immunother. 2009 Jan;58(1):49-59
18446337
J Immunol. 2009 May 15;182(10):6562-8
19414811
Front Genet. 2012 Aug 08;3:142
22891074
Oncotarget. 2016 Oct 25;7(43):69097-69110
27533245
Am J Hum Genet. 2010 Jul 9;87(1):139-45
20598278
Oncotarget. 2016 Feb 9;7(6):6353-68
26840454
Genet Epidemiol. 2006 Nov;30(7):636-43
16986161