Large-Scale Evaluation of Common Variation in Regulatory T Cell-Related Genes and Ovarian Cancer Outcome

Bridget Charbonneau; Kirsten B Moysich; Kimberly R Kalli; Ann L Oberg; Robert A Vierkant; Zachary C Fogarty; Matthew S Block; Matthew J Maurer; Krista M Goergen; Brooke L Fridley; Julie M Cunningham; David N Rider; Claudia Preston; Lynn C Hartmann; Kate Lawrenson; Chen Wang; Jonathan Tyrer; Honglin Song; Anna deFazio; Sharon E Johnatty; Jennifer A Doherty; Catherine M Phelan; Thomas A Sellers; Starr M Ramirez; Allison F Vitonis; Kathryn L Terry; David Van Den Berg; Malcolm C Pike; Anna H Wu; Andrew Berchuck; Aleksandra Gentry-Maharaj; Susan J Ramus; Brenda Diergaarde; Howard Shen; Allan Jensen; Janusz Menkiszak; Cezary Cybulski; Jan Lubiński; Argyrios Ziogas; Joseph H Rothstein; Valerie McGuire; Weiva Sieh; Jenny Lester; Christine Walsh; Ignace Vergote; Sandrina Lambrechts; Evelyn Despierre; Montserrat Garcia-Closas; Hannah Yang; Louise A Brinton; Beata Spiewankiewicz; Iwona K Rzepecka; Agnieszka Dansonka-Mieszkowska; Petra Seibold; Anja Rudolph; Lisa E Paddock; Irene Orlow; Lene Lundvall; Sara H Olson; Claus K Hogdall; Ira Schwaab; Andreas du Bois; Philipp Harter; James M Flanagan; Robert Brown; James Paul; Arif B Ekici; Matthias W Beckmann; Alexander Hein; Diana Eccles; Galina Lurie; Laura E Hays; Yukie T Bean; Tanja Pejovic; Marc T Goodman; Ian Campbell; Peter A Fasching; Gottfried Konecny; Stanley B Kaye; Florian Heitz; Estrid Hogdall; Elisa V Bandera; Jenny Chang-Claude; Jolanta Kupryjanczyk; Nicolas Wentzensen; Diether Lambrechts; Beth Y Karlan; Alice S Whittemore; Hoda Anton Culver; Jacek Gronwald; Douglas A Levine; Susanne K Kjaer; Usha Menon; Joellen M Schildkraut; Celeste Leigh Pearce; Daniel W Cramer; Mary Anne Rossing; Georgia Chenevix-Trench; Paul D.P Pharoah; Simon A Gayther; Roberta B Ness; Kunle Odunsi; Lara E Sucheston; AOCS Grp; Keith L Knutson; Ellen L Goode

doi:10.1158/2326-6066.CIR-13-0136

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Large-Scale Evaluation of Common Variation in Regulatory T Cell-Related Genes and Ovarian Cancer Outcome

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Large-Scale Evaluation of Common Variation in Regulatory T Cell-Related Genes and Ovarian Cancer Outcome

Bridget Charbonneau, Kirsten B Moysich, Kimberly R Kalli, Ann L Oberg, Robert A Vierkant, Zachary C Fogarty, Matthew S Block, Matthew J Maurer, Krista M Goergen, Brooke L Fridley, …

Cancer immunology research, Vol.2(4), pp.332-340

04/2014

DOI: https://doi.org/10.1158/2326-6066.CIR-13-0136

PMCID: PMC4000890

PMID: 24764580

Abstract

clear cell

endometrioid

gynecologic neoplasms

single nucleotide polymorphism

The presence of regulatory T cells (Tregs) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag SNPs in 25 Treg-associated genes ( CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2 , and TGFBR3 ) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR=1.42, 95% CI: 1.22–1.64; p=5.7 × 10 −6 ], rs791587 [HR=1.36, 95% CI:1.17–1.57; p=6.2 × 10 −5 ], rs2476491 [HR=1.40, 95% CI: 1.191.64; p=5.6 × 10 −5 ], and rs10795763 [HR=1.35, 95% CI: 1.17–1.57; p=7.9 × 10 −5 ], and for clear cell carcinoma and CTLA4 SNP rs231775 [HR=0.67, 95% CI: 0.54–0.82; p=9.3 × 10 −5 ] after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs appear to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid EOC.

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Title: Large-Scale Evaluation of Common Variation in Regulatory T Cell-Related Genes and Ovarian Cancer Outcome
Creators: Bridget Charbonneau - Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA
Kirsten B Moysich - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
Kimberly R Kalli - Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA
Ann L Oberg - Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
Robert A Vierkant - Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
Zachary C Fogarty - Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
Matthew S Block - Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA
Matthew J Maurer - Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
Krista M Goergen - Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
Brooke L Fridley - Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA
Julie M Cunningham - Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN, USA
David N Rider - Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
Claudia Preston - Department of Immunology, Mayo Clinic, Rochester, MN, USA
Lynn C Hartmann - Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA
Kate Lawrenson - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Chen Wang - Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
Jonathan Tyrer - Department of Oncology, University of Cambridge, Cambridge, UK
Honglin Song - Department of Oncology, University of Cambridge, Cambridge, UK
Anna deFazio - Department of Gynaecological Oncology, Westmead Hospital and Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead, Australia
Sharon E Johnatty - Cancer Division, Queensland Institute of Medical Research, Herston, QLD, Australia
Jennifer A Doherty - Section of Biostatistics and Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
Catherine M Phelan - Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA
Thomas A Sellers - Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA
Starr M Ramirez - Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA
Allison F Vitonis - Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Kathryn L Terry - Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
David Van Den Berg - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Malcolm C Pike - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Anna H Wu - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Andrew Berchuck - Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA
Aleksandra Gentry-Maharaj - Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, UK
Susan J Ramus - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Brenda Diergaarde - Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA
Howard Shen - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Allan Jensen - Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
Janusz Menkiszak - Department of Surgical Gynecology and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland
Cezary Cybulski - International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
Jan Lubiński - International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
Argyrios Ziogas - Department of Epidemiology, Center for Cancer Genetics Research and Prevention, School of Medicine, University of California Irvine, Irvine, CA, USA
Joseph H Rothstein - Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Palo Alto, CA, USA
Valerie McGuire - Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Palo Alto, CA, USA
Weiva Sieh - Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Palo Alto, CA, USA
Jenny Lester - Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Christine Walsh - Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Ignace Vergote - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Leuven Cancer Institute, University Hospitals Leuven, Belgium
Sandrina Lambrechts - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Leuven Cancer Institute, University Hospitals Leuven, Belgium
Evelyn Despierre - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Leuven Cancer Institute, University Hospitals Leuven, Belgium
Montserrat Garcia-Closas - Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK and Breakthrough Breast Cancer Research Centre, London, UK
Hannah Yang - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Louise A Brinton - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Beata Spiewankiewicz - Department of Gynecologic Oncology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Iwona K Rzepecka - Department of Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Agnieszka Dansonka-Mieszkowska - Department of Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Petra Seibold - German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany
Anja Rudolph - German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany
Lisa E Paddock - New Jersey Department of Health, Trenton, NJ, USA
Irene Orlow - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Lene Lundvall - Department of Gynaecology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Sara H Olson - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Claus K Hogdall - Department of Gynaecology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Ira Schwaab - Institut für Humangenetik Wiesbaden, Wiesbaden, Germany
Andreas du Bois - Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
Philipp Harter - Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
James M Flanagan - Department of Surgery and Cancer, Imperial College London, London, UK
Robert Brown - Department of Surgery and Cancer, Imperial College London, London, UK
James Paul - The Beatson West of Scotland Cancer Centre, Glasgow, UK
Arif B Ekici - Institute of Human Genetics, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany
Matthias W Beckmann - University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, Germany
Alexander Hein - University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, Germany
Diana Eccles - Faculty of Medicine, University of Southampton, University Hospital Southampton, UK
Galina Lurie - Cancer Epidemiology Program, University of Hawaii Cancer Center, HI, USA
Laura E Hays - Department of Hematology and Oncology and the Knight Cancer Institute, Portland, OR, USA
Yukie T Bean - Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA
Tanja Pejovic - Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA
Marc T Goodman - Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Ian Campbell - Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia
Peter A Fasching - University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, Germany
Gottfried Konecny - Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, SA
Stanley B Kaye - Division of Clinical Studies, The Institute of Cancer Research and the Royal Marsden Hospital, Sutton, UK
Florian Heitz - Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
Estrid Hogdall - Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
Elisa V Bandera - Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA
Jenny Chang-Claude - German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany
Jolanta Kupryjanczyk - Department of Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Nicolas Wentzensen - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Diether Lambrechts - Vesalius Research Center, VIB, Leuven, Belgium
Beth Y Karlan - Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Alice S Whittemore - Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Palo Alto, CA, USA
Hoda Anton Culver - Department of Epidemiology, Center for Cancer Genetics Research and Prevention, School of Medicine, University of California Irvine, Irvine, CA, USA
Jacek Gronwald - International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
Douglas A Levine - Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Susanne K Kjaer - Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
Usha Menon - Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, UK
Joellen M Schildkraut - Cancer Prevention, Detection and Control Research Program, Duke Cancer Institute, Durham, NC, USA
Celeste Leigh Pearce - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Daniel W Cramer - Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Mary Anne Rossing - Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Georgia Chenevix-Trench - Cancer Division, Queensland Institute of Medical Research, Herston, QLD, Australia
Paul D.P Pharoah - Department of Oncology, University of Cambridge, Cambridge, UK
Simon A Gayther - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Roberta B Ness - The University of Texas School of Public Health, Houston, TX, USA
Kunle Odunsi - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
Lara E Sucheston - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
AOCS Grp
Keith L Knutson - Department of Immunology, Mayo Clinic, Rochester, MN, USA
Ellen L Goode - Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA
Publication Details: Cancer immunology research, Vol.2(4), pp.332-340
Date published: 04/2014
Academic Unit: Graduate School - Newark; Earth and Environmental Science (SASN); Cancer Epidemiology and Health Outcomes; Office of Summer and Winter Sessions
Language: English
Resource Type: Journal article
Identifiers: 991031664336904646