Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

Hampras SS, Sucheston-Campbell LE, Cannioto R, Chang-Claude J, Modugno F, Doerk T, Hillemanns P, Preus L, Knutson KL, Wallace PK, Hong CC, Friel G, Davis W, Nesline M, Pearce CL, Kelemen LE, Goodman MT, Bandera EV, Terry KL, Schoof N, Eng KH, Clay A, Singh PK, Joseph JM, Aben KKH, Anton-Culver H, Antonenkova N, Baker H, Bean Y, Beckmann M, Bisogna M, Bjorge L, Bogdanova N, Brinton LA, Brooks-Wilson A, Bruinsma F, Butzow R, Campbell IG, Carty K, Cook LS, Cramer DW, Cybulski C, Dansonka-Mieszkowska A, Dennis J, Despierre E, Dicks E, Doherty JA, Du Bois A, Duerst M, Easton D, Eccles D, Edwards RP, Ekici AB, Fasching P, Fridley BL, Gao YT, Gentry-Maharaj A, Giles GG, Glasspool R, Gronwald J, Harrington P, Harter P, Hasmad HN, Hein A, Heitz F, Hildebrandt MAT, Hogdall C, Hogdall E, Hosono S, Iversen ES, Jakubowska A, Jensen A, Ji BT, Karlan BY, Kellar M, Kelley JL, Kiemeney LA, Klapdor R, Kolomeyevskaya N, Krakstad C, Kjaer SK, Kruszka B, Kupryjanczyk J, Lambrechts D, Lambrechts S, Le ND, Lee AW, Lele S, Leminen A, Lester J, Levine DA, Liang D, Lissowska J, Liu S, Lu K, Lubinski J, Lundvall L, Massuger LFAG, Matsuo K, Mcguire V, Mclaughlin JR, Mcneish I, Menon U, Moes-Sosnowska J, Narod SA, Nedergaard L, Nevanlinna H, Nickels S, Olson SH, Orlow I, Weber RP, Paul J, Pejovic T, Pelttari LM, Perkins B, Permuth-Wey J, Pike MC, Plisiecka-Halasa J, Poole EM, Risch HA, Rossing MA, Rothstein JH, Rudolph A, Runnebaum IB, Rzepecka IK, Salvesen HB, Schernhammer E, Schmitt K, Schwaab I, Shu XO, Shvetsov YB, Siddiqui N, Sieh W, Song H, Southey MC, Tangen IL, Teo SH, Thompson PJ, Timorek A, Tsai YY, Tworoger SS, Tyrer J, Van Altena AM, Vergote I, Vierkant RA, Walsh C, Wang-Gohrke S, Wentzensen N, Whittemore AS, Wicklund KG, Wilkens LR, Wu AH, Wu X, Woo YL, Yang H, Zheng W, Ziogas A, Gayther SA, Ramus SJ, Sellers TA, Schildkraut JM, Phelan CM, Berchuck A, Chenevix-Trench G, Cunningham JM, Pharoah PP, Ness RB, Odunsi K, Goode EL, Moysich KB (2016)

Publication Type: Journal article

Publication year: 2016

Journal

DOI: 10.18632/oncotarget.10215

Abstract

Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer.In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients.The most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with TGFBR2 (p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 (p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA (p = 0.035, endometrioid and mucinous), LGALS1 (p = 0.03, mucinous), STAT5B (p = 0.022, clear cell), TGFBR1 (p = 0.021 endometrioid) and TGFBR2 (p = 0.017 and p = 0.025, endometrioid and mucinous, respectively).Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.

Authors with CRIS profile

Involved external institutions

Friedrich-Schiller-Universität Jena Germany (DE) Brigham and Women's Hospital (BWH) United States (USA) (US) Rutgers Cancer Institute of New Jersey United States (USA) (US) Cedars-Sinai Medical Center United States (USA) (US) The University of Melbourne Australia (AU) University of Cambridge United Kingdom (GB) Stanford University United States (USA) (US) Glasgow Royal Infirmary (GRI) United Kingdom (GB) Haukeland University Hospital / Haukeland universitetssykehus Norway (NO) University of Southern California (USC) United States (USA) (US) Roswell Park Cancer Institute United States (USA) (US) Mayo Clinic United States (USA) (US) University of Texas MD Anderson Cancer Center United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Duke University United States (USA) (US) H. Lee Moffitt Cancer Center & Research Institute United States (USA) (US) Aichi Cancer Center Research Institute Japan (JP) Radboud University Nijmegen Netherlands (NL) University of Copenhagen Denmark (DK) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Memorial Sloan Kettering Cancer Center United States (USA) (US) Helsingin yliopisto / University of Helsinki Finland (FI) British Columbia Cancer Agency Canada (CA) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) University of Pittsburgh United States (USA) (US) Oregon Health and Science University (OSHU) United States (USA) (US) Danish Cancer Society Denmark (DK) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Kliniken Essen-Mitte Germany (DE) Cancer Research Initiatives Foundation (CARIF) / Cancer Research Malaysia (CRM) Malaysia (MY) University of Glasgow United Kingdom (GB) Cancer Council Victoria Australia (AU) University College London (UCL) United Kingdom (GB) Shanghai Cancer Institute / 上海市肿瘤研究所 China (CN) University of Kansas (KU) United States (USA) (US) Princess Anne Hospital United Kingdom (GB) Dartmouth College United States (USA) (US) University of New Mexico (UNM) / Universidad de Nuevo México United States (USA) (US) Peter MacCallum Cancer Centre Australia (AU) National Cancer Institute (NCI) United States (USA) (US) Texas Southern University (TSU) United States (USA) (US) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology Belarus (BY) University of California Irvine United States (USA) (US) Karolinska Institute Sweden (SE) Alberta Health Services (AHS) Canada (CA) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Ohio State University United States (USA) (US) Vanderbilt University United States (USA) (US) University of Malaya (UM) / Universiti Malaya Malaysia (MY) University of Hawaii (U.H.) United States (USA) (US) Fred Hutchinson Cancer Research Center United States (USA) (US) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu Poland (PL) Institut für Humangenetik Wiesbaden Germany (DE) Harvard University United States (USA) (US) Yale University United States (USA) (US) Women's College Hospital Canada (CA) Mount Sinai Hospital (MSH) Canada (CA)

How to cite

APA:

Hampras, S.S., Sucheston-Campbell, L.E., Cannioto, R., Chang-Claude, J., Modugno, F., Doerk, T.,... Moysich, K.B. (2016). Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer. Oncotarget. https://doi.org/10.18632/oncotarget.10215

MLA:

Hampras, Shalaka S., et al. "Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer." Oncotarget (2016).

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