Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome

Charbonneau B, Moysich KB, Kalli KR, Oberg AL, Vierkant RA, Fogarty ZC, Block MS, Maurer MJ, Goergen KM, Fridley BL, Cunningham JM, Rider DN, Preston C, Hartmann LC, Lawrenson K, Wang C, Tyrer J, Song H, Defazio A, Johnatty SE, Doherty JA, Phelan CM, Sellers TA, Ramirez SM, Vitonis AF, Terry KL, Van Den Berg D, Pike MC, Wu AH, Berchuck A, Gentry-Maharaj A, Ramus SJ, Diergaarde B, Shen H, Jensen A, Menkiszak J, Cybulski C, Lubinski J, Ziogas A, Rothstein JH, Mcguire V, Sieh W, Lester J, Walsh C, Vergote I, Lambrechts S, Despierre E, Garcia-Closas M, Yang H, Brinton LA, Spiewankiewicz B, Rzepecka IK, Dansonka-Mieszkowska A, Seibold P, Rudolph A, Paddock LE, Orlow I, Lundvall L, Olson SH, Hogdall CK, Schwaab I, Du Bois A, Harter P, Flanagan JM, Brown R, Paul J, Ekici AB, Beckmann M, Hein A, Eccles D, Lurie G, Hays LE, Bean YT, Pejovic T, Goodman MT, Campbell I, Fasching P, Konecny G, Kaye SB, Heitz F, Hogdall E, Bandera EV, Chang-Claude J, Kupryjanczyk J, Wentzensen N, Lambrechts D, Karlan BY, Whittemore AS, Culver HA, Gronwald J, Levine DA, Kjaer SK, Menon U, Schildkraut JM, Pearce CL, Cramer DW, Rossing MA, Chenevix-Trench G, Pharoah PDP, Gayther SA, Ness RB, Odunsi K, Sucheston LE, Knutson KL, Goode EL (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Book Volume: 2

Pages Range: 332-40

Journal Issue: 4

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

Abstract

The presence of regulatory T cells (Treg) 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 single-nucleotide polymorphisms (SNP) 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% confidence interval (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, 1.19-1.64; 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 seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer.

Authors with CRIS profile

Involved external institutions

University of Copenhagen Denmark (DK) Mayo Clinic United States (USA) (US) University of Kansas (KU) United States (USA) (US) Oregon Health and Science University (OSHU) United States (USA) (US) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) University of Southern California (USC) United States (USA) (US) Peter MacCallum Cancer Centre Australia (AU) Duke University United States (USA) (US) Beatson West of Scotland Cancer Centre (BWSCC) United Kingdom (GB) Cedars-Sinai Medical Center United States (USA) (US) Rigshospitalet Denmark (DK) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) National Cancer Institute (NCI) United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) University of Pittsburgh United States (USA) (US) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Brigham and Women's Hospital (BWH) United States (USA) (US) Kliniken Essen-Mitte Germany (DE) Roswell Park Cancer Institute United States (USA) (US) University of California Irvine United States (USA) (US) Stanford University United States (USA) (US) Institute for Oncology Ljubljana (OIL) Slovenia (SI) University of Southampton United Kingdom (GB) H. Lee Moffitt Cancer Center & Research Institute United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) University College London (UCL) United Kingdom (GB) University of Medicine and Dentistry of New Jersey (UMDNJ) United States (USA) (US) Royal Marsden Hospital / The Royal Marsden NHS Foundation Trust United Kingdom (GB) University of Cambridge United Kingdom (GB) Dartmouth College United States (USA) (US) University of California Los Angeles (UCLA) United States (USA) (US) Imperial College London / The Imperial College of Science, Technology and Medicine United Kingdom (GB) University of Sydney (USYD) Australia (AU)

How to cite

APA:

Charbonneau, B., Moysich, K.B., Kalli, K.R., Oberg, A.L., Vierkant, R.A., Fogarty, Z.C.,... Goode, E.L. (2014). Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome. Cancer Immunology Research, 2(4), 332-40. https://doi.org/10.1158/2326-6066.CIR-13-0136

MLA:

Charbonneau, Bridget, et al. "Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome." Cancer Immunology Research 2.4 (2014): 332-40.

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