Title: Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome
Authors: Charbonneau, Bridget ×
Moysich, Kirsten B
Kalli, Kimberly R
Oberg, Ann L
Vierkant, Robert A
Fogarty, Zachary C
Block, Matthew S
Maurer, Matthew J
Goergen, Krista M
Fridley, Brooke L
Cunningham, Julie M
Rider, David N
Preston, Claudia
Hartmann, Lynn C
Lawrenson, Kate
Wang, Chengjun
Tyrer, Jonathan
Song, Honglin
deFazio, Anna
Johnatty, Sharon E
Doherty, Jennifer A
Phelan, Catherine M
Sellers, Thomas A
Ramirez, Starr M
Vitonis, Allison F
Terry, Kathryn L
Van Den Berg, David
Pike, Malcolm C
Wu, Anna H
Berchuck, Andrew
Gentry-Maharaj, Aleksandra
Ramus, Susan J
Diergaarde, Brenda
Shen, Howard
Jensen, Allan
Menkiszak, Janusz
Cybulski, Cezary
Lubiłski, Jan
Ziogas, Argyrios
Rothstein, Joseph H
McGuire, Valerie
Sieh, Weiva
Lester, Jenny
Walsh, Christine
Vergote, Ignace
Lambrechts, Sandrina
Despierre, Evelyn
Garcia-Closas, Montserrat
Yang, Hannah
Brinton, Louise A
Spiewankiewicz, Beata
Rzepecka, Iwona K
Dansonka-Mieszkowska, Agnieszka
Seibold, Petra
Rudolph, Anja
Paddock, Lisa E
Orlow, Irene
Lundvall, Lene
Olson, Sara H
Hogdall, Claus K
Schwaab, Ira
du Bois, Andreas
Harter, Philipp
Flanagan, James M
Brown, Robert
Paul, James
Ekici, Arif B
Beckmann, Matthias W
Hein, Alexander
Eccles, Diana
Lurie, Galina
Hays, Laura E
Bean, Yukie T
Pejovic, Tanja
Goodman, Marc T
Campbell, Ian
Fasching, Peter A
Konecny, Gottfried
Kaye, Stanley B
Heitz, Florian
Hogdall, Estrid
Bandera, Elisa V
Chang-Claude, Jenny
Kupryjanczyk, Jolanta
Wentzensen, Nicolas
Lambrechts, Diether
Karlan, Beth Y
Whittemore, Alice S
Culver, Hoda Anton
Gronwald, Jacek
Levine, Douglas A
Kjaer, Susanne K
Menon, Usha
Schildkraut, Joellen M
Pearce, Celeste Leigh
Cramer, Daniel W
Rossing, Mary Anne
Chenevix-Trench, Georgia
AOCS group
Pharoah, Paul D P
Gayther, Simon A
Ness, Roberta B
Odunsi, Kunle
Sucheston, Lara E
Knutson, Keith L
Goode, Ellen L #
Issue Date: Apr-2014
Publisher: American Association for Cancer Research
Series Title: Cancer Immunology Research vol:2 issue:4 pages:332-340
Article number: 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.
ISSN: 2326-6066
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gynaecological Oncology
De Wulf-Mansion Centre for Ancient, Medieval and Renaissance Philosophy
Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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