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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome

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  • 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 Lubiłski
  • Argyrios Ziogas
  • Joseph H Rothstein
  • Valerie McGuire
  • Weiva Sieh
  • Jenny Lester
  • Christine Walsh
  • Ignace Vergote
  • Sandrina Lambrechts
  • Lene Lundvall
  • Claus K Hogdall
  • Estrid Hogdall
  • Susanne K Kjaer
  • AOCS group
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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.

Original languageEnglish
JournalCancer immunology research
Volume2
Issue number4
Pages (from-to)332-40
Number of pages9
DOIs
Publication statusPublished - Apr 2014

    Research areas

  • Female, Gene Expression, Gene Expression Profiling, Genetic Predisposition to Disease, Genetic Variation, Germ-Line Mutation, Humans, Interleukin-2 Receptor alpha Subunit, Neoplasm Grading, Neoplasm Invasiveness, Ovarian Neoplasms, Patient Outcome Assessment, Polymorphism, Single Nucleotide, Prognosis, T-Lymphocytes, Regulatory

ID: 44867033