No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival

Lara E Sucheston-Campbell¹, Rikki Cannioto², Alyssa I Clay³, John Lewis Etter², Kevin H Eng⁴, Song Liu⁴, Sebastiano Battaglia⁵, Qiang Hu⁴, J Brian Szender⁶, Albina Minlikeeva², Janine M Joseph², Paul Mayor⁶, Scott I Abrams⁷, Brahm H Segal^{7

8}, Paul K Wallace⁹, Kah Teong Soh⁹, Emese Zsiros⁶, Hoda Anton-Culver¹⁰, Elisa V Bandera¹¹, Matthias W Beckmann¹², Andrew Berchuck¹³, Line Bjorge^{14

15}, Amanda Bruegl¹⁶, Ian G Campbell^{17

18}, Shawn Patrice Campbell¹⁶, Georgia Chenevix-Trench, Daniel W Cramer^{19

20}, Agnieszka Dansonka-Mieszkowska²¹, Fanny Dao²², Brenda Diergaarde²³, Thilo Doerk²⁴, Jennifer A Doherty²⁵, Andreas du Bois^{26

27}, Diana Eccles^{28

29}, Svend Aage Engelholm³⁰, Peter A Fasching¹², Simon A Gayther^{31

32}, Aleksandra Gentry-Maharaj³³, Rosalind M Glasspool³⁴, Marc T Goodman^{35

36}, Jacek Gronwald³⁷, Philipp Harter²⁶, Alexander Hein¹², Florian Heitz^{26

27}, Peter Hillemmanns²⁴, Claus Høgdall³⁸, Estrid V S Høgdall^{39

40}, Tomasz Huzarski³⁷, Allan Jensen³⁹, Sharon E Johnatty⁴¹, Audrey Jung^{42

43}, Beth Y Karlan⁴⁴, Reudiger Klapdor²⁴, Tomasz Kluz⁴⁵, Bożena Konopka²¹, Susanne Krüger Kjær^{38

39}, Jolanta Kupryjanczyk²¹, Diether Lambrechts⁴⁶, Jenny Lester⁴⁴, Jan Lubiński³⁷, Douglas A Levine²², Lene Lundvall⁴⁷, Valerie McGuire⁴⁸, Iain A McNeish⁴⁹, Usha Menon³³, Francesmary Modugno^{23

50

51}, Roberta B Ness⁵², Sandra Orsulic⁴⁴, James Paul³⁴, Celeste Leigh Pearce^{53

54}, Tanja Pejovic^{16

55}, Paul Pharoah^{56

57}, Susan J Ramus^{58

59}, Joseph Rothstein⁴⁸, Mary Anne Rossing^{60

61}, Matthias Rübner¹², Joellen M Schildkraut⁶², Barbara Schmalfeldt⁶³, Ira Schwaab⁶⁴, Nadeem Siddiqui⁶⁵, Weiva Sieh^{66

67}, Piotr Sobiczewski⁶⁸, Honglin Song⁵⁶, Kathryn L Terry^{19

20}, Els Van Nieuwenhuysen⁶⁹, Adriaan Vanderstichele⁶⁹, Ignace Vergote⁶⁹, Christine S Walsh⁴⁴, Penelope M Webb⁷⁰, Nicolas Wentzensen⁷¹, Alice S Whittemore⁴⁸, Anna H Wu⁵⁴, Argyrios Ziogas⁷², Kunle Odunsi⁶, Jenny Chang-Claude^{42

43}, Ellen L Goode⁷³, Kirsten B Moysich⁷⁴; Australian Ovarian Cancer Study

Affiliations

¹ College of Pharmacy, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio.
² Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
³ Cancer Genetic Epidemiology, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
⁴ Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York.
⁵ Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York.
⁶ Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York.
⁷ Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York.
⁸ Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York.
⁹ Department of Flow & Image Cytometry, Roswell Park Cancer Institute, Buffalo, New York.
¹⁰ Genetic Epidemiology Research Institute, School of Medicine, University of California Irvine, Irvine, California.
¹¹ Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
¹² Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
¹³ Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina.
¹⁴ Department of Gynecology and Obstetrics, Haukeland University Horpital, Bergen, Norway.
¹⁵ Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway.
¹⁶ Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon.
¹⁷ Cancer Genetics Laboratory, East Melbourne, Australia.
¹⁸ Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
¹⁹ Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, Massachusetts.
²⁰ Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
²¹ Department of Pathology and Laboratory Diagnostics, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
²² Gynecologic Oncology, Laura and Isaac Pearlmutter Cancer Center, NYU Langone Medical Center, New York, New York.
²³ Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
²⁴ Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Niedersachsen, Germany.
²⁵ Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
²⁶ Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany.
²⁷ Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany.
²⁸ Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
²⁹ Wessex Clinical Genetics Service, Southampton University Hospitals Trust, Southampton, United Kingdom.
³⁰ Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
³¹ Center for Cancer Prevention and Translational Genomics, Cedars-Sinai Medical Center, Los Angeles, California.
³² Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.
³³ Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
³⁴ The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
³⁵ Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
³⁶ Department of Biomedical Sciences, Community and Population Health Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
³⁷ Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
³⁸ Department of Gynaecology, Rigshospitalet, University of Copenhagen, Herlev, Denmark.
³⁹ Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
⁴⁰ Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
⁴¹ Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, Herston, Australia.
⁴² Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
⁴³ University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Heidelberg, Germany.
⁴⁴ Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
⁴⁵ Clinic of Obstetrics and Gynecology, Institute of Midwifery and Emergency Medicine, Faculty of Medicine, University of Rzeszów, Rzeszów, Poland.
⁴⁶ Department of Oncology, Laboratory for Translational Genetics, Vesalius Research Center, University of Leuven, Leuven, Belgium.
⁴⁷ Department of Gynecology, The Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
⁴⁸ Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, California.
⁴⁹ Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow, United Kingdom.
⁵⁰ Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
⁵¹ Ovarian Cancer Center of Excellence, Womens Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
⁵² The University of Texas School of Public Health, Houston, Texas.
⁵³ Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan.
⁵⁴ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
⁵⁵ Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
⁵⁶ Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
⁵⁷ Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
⁵⁸ School of Women's and Children's Health, University of New South Wales, New South Wales, Australia.
⁵⁹ The Kinghorn Cancer Centre, Garvan Institute of Medical Research, New South Wales, New South Wales, Australia.
⁶⁰ Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
⁶¹ Department of Epidemiology, University of Washington, Seattle, Washington.
⁶² Department of Public Health Sciences, The University of Virginia, Charlottesville, Virginia.
⁶³ Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁶⁴ Praxis für Humangenetik, Wiesbaden, Germany.
⁶⁵ Department of Gynaecological Oncology, Glasgow Royal Infirmary, Glasgow, United Kingdom.
⁶⁶ Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.
⁶⁷ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
⁶⁸ Department of Gynecologic Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
⁶⁹ Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
⁷⁰ Population Health Department, QIMR Berghofer Medical Research Institute, Herston, Australia.
⁷¹ Division of Cancer Epidemiology and Genetics, NCI, Bethesda, Maryland.
⁷² Department of Epidemiology, University of California Irvine, Irvine, California.
⁷³ Department of Health Science Research, Mayo Clinic, Rochester, Minnesota.
⁷⁴ Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York. kirsten.moysich@roswellpark.org.

PMID: 27677730
PMCID: PMC5500198
DOI: 10.1158/1055-9965.EPI-16-0631

Meta-Analysis

No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival

Lara E Sucheston-Campbell et al. Cancer Epidemiol Biomarkers Prev. 2017 Mar.

. 2017 Mar;26(3):420-424.

doi: 10.1158/1055-9965.EPI-16-0631. Epub 2016 Sep 27.

Authors

Affiliations

¹ College of Pharmacy, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio.
² Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
³ Cancer Genetic Epidemiology, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
⁴ Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York.
⁵ Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York.
⁶ Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York.
⁷ Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York.
⁸ Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York.
⁹ Department of Flow & Image Cytometry, Roswell Park Cancer Institute, Buffalo, New York.
¹⁰ Genetic Epidemiology Research Institute, School of Medicine, University of California Irvine, Irvine, California.
¹¹ Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
¹² Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
¹³ Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina.
¹⁴ Department of Gynecology and Obstetrics, Haukeland University Horpital, Bergen, Norway.
¹⁵ Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway.
¹⁶ Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon.
¹⁷ Cancer Genetics Laboratory, East Melbourne, Australia.
¹⁸ Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
¹⁹ Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, Massachusetts.
²⁰ Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
²¹ Department of Pathology and Laboratory Diagnostics, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
²² Gynecologic Oncology, Laura and Isaac Pearlmutter Cancer Center, NYU Langone Medical Center, New York, New York.
²³ Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
²⁴ Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Niedersachsen, Germany.
²⁵ Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
²⁶ Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany.
²⁷ Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany.
²⁸ Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
²⁹ Wessex Clinical Genetics Service, Southampton University Hospitals Trust, Southampton, United Kingdom.
³⁰ Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
³¹ Center for Cancer Prevention and Translational Genomics, Cedars-Sinai Medical Center, Los Angeles, California.
³² Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.
³³ Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
³⁴ The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
³⁵ Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
³⁶ Department of Biomedical Sciences, Community and Population Health Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
³⁷ Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
³⁸ Department of Gynaecology, Rigshospitalet, University of Copenhagen, Herlev, Denmark.
³⁹ Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
⁴⁰ Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
⁴¹ Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, Herston, Australia.
⁴² Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
⁴³ University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Heidelberg, Germany.
⁴⁴ Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
⁴⁵ Clinic of Obstetrics and Gynecology, Institute of Midwifery and Emergency Medicine, Faculty of Medicine, University of Rzeszów, Rzeszów, Poland.
⁴⁶ Department of Oncology, Laboratory for Translational Genetics, Vesalius Research Center, University of Leuven, Leuven, Belgium.
⁴⁷ Department of Gynecology, The Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
⁴⁸ Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, California.
⁴⁹ Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow, United Kingdom.
⁵⁰ Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
⁵¹ Ovarian Cancer Center of Excellence, Womens Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
⁵² The University of Texas School of Public Health, Houston, Texas.
⁵³ Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan.
⁵⁴ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
⁵⁵ Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
⁵⁶ Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
⁵⁷ Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
⁵⁸ School of Women's and Children's Health, University of New South Wales, New South Wales, Australia.
⁵⁹ The Kinghorn Cancer Centre, Garvan Institute of Medical Research, New South Wales, New South Wales, Australia.
⁶⁰ Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
⁶¹ Department of Epidemiology, University of Washington, Seattle, Washington.
⁶² Department of Public Health Sciences, The University of Virginia, Charlottesville, Virginia.
⁶³ Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁶⁴ Praxis für Humangenetik, Wiesbaden, Germany.
⁶⁵ Department of Gynaecological Oncology, Glasgow Royal Infirmary, Glasgow, United Kingdom.
⁶⁶ Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.
⁶⁷ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
⁶⁸ Department of Gynecologic Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
⁶⁹ Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
⁷⁰ Population Health Department, QIMR Berghofer Medical Research Institute, Herston, Australia.
⁷¹ Division of Cancer Epidemiology and Genetics, NCI, Bethesda, Maryland.
⁷² Department of Epidemiology, University of California Irvine, Irvine, California.
⁷³ Department of Health Science Research, Mayo Clinic, Rochester, Minnesota.
⁷⁴ Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York. kirsten.moysich@roswellpark.org.

PMID: 27677730
PMCID: PMC5500198
DOI: 10.1158/1055-9965.EPI-16-0631

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.

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Conflict of interest statement

CONFLICT OF INTEREST STATEMENT

M. Goodman was a consultant for Johnson and Johnson

Figures

**Figure 1**
These five concentric circles are circular standard Manhattan plots. The chromosome is on the outer circle, −log10 p-values are on the (vertical) y-axis with each circle representing the p-value from single SNP tests of association with overall survival adjusted for age, stage and grade. The Manhattan plots are as follows: A) all ovarian cancer cases B) high grade serous C) mucinous cell D) endometrioid and E) clear cell. The red dashed line designates p=.01, −log10(p-value)=2, with all red-colored SNPs above that line reflecting SNPs p<.01.

See this image and copyright information in PMC

References

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1. Collaborative Oncological Gene-environment Study. http://cogseu.org/
1. Hampras S, Sucheston-Campbell L, Cannioto R, Chang-Claude J, Modugno F, Dörk T, et al. Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer. Oncotarget. 2016 - PMC - PubMed
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No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival

Affiliations

No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

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Medical