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Title: Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome.
Authors: 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,  Lubiłski 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 MW,  Hein A,  Eccles D,  Lurie G,  Hays LE,  Bean YT,  Pejovic T,  Goodman MT,  Campbell I,  Fasching PA,  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,  AOCS group,  ACS,  Pharoah PD,  Gayther SA,  Ness RB,  Odunsi K,  Sucheston LE,  Knutson KL,  Goode EL
Journal: Cancer Immunol Res
Date: 2014 Apr
Branches: MEB, OD
PubMed ID: 24764580
PMC ID: PMC4000890
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.