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

Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome
Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome
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
2326-6066
332-340
Charbonneau, B.
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Moysich, K.B.
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Kalli, K.R.
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Oberg, A.L.
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Vierkant, R.A.
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Fogarty, Z.C.
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Block, M.S.
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Maurer, M.J.
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Goergen, K.M.
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Fridley, B.L.
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Cunningham, J.M.
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Rider, D.N.
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Preston, C.
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Hartmann, L.C.
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Lawrenson, K.
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Wang, C.
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Tyrer, J.
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Song, H.
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deFazio, A.
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Johnatty, S.E.
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Doherty, J.A.
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Phelan, C.M.
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Sellers, T.A.
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Ramirez, S.M.
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Vitonis, A.F.
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Terry, K.L.
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Van Den Berg, D.
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Pike, M.C.
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Wu, A.H.
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Berchuck, A.
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Gentry-Maharaj, A.
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Ramus, S.J.
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Diergaarde, B.
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Shen, H.
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Jensen, A.
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Menkiszak, J.
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Cybulski, C.
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Lubi ski, J.
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Ziogas, A.
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Rothstein, J.H.
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McGuire, V.
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Sieh, W.
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Lester, J.
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Walsh, C.
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Vergote, I.
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Lambrechts, S.
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Despierre, E.
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Garcia-Closas, M.
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Yang, H.
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Brinton, L.A.
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Spiewankiewicz, B.
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Rzepecka, I.K.
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Dansonka-Mieszkowska, A.
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Seibold, P.
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Rudolph, A.
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Paddock, L.E.
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Orlow, I.
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Lundvall, L.
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Olson, S.H.
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Hogdall, C.K.
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Schwaab, I.
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du Bois, A.
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Harter, P.
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Flanagan, J.M.
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Brown, R.
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Paul, J.
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Ekici, A.B.
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Beckmann, M.W.
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Hein, A.
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Eccles, D.
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Lurie, G.
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Hays, L.E.
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Bean, Y.T.
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Pejovic, T.
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Goodman, M.T.
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Campbell, I.
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Fasching, P.A.
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Konecny, G.
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Kaye, S.B.
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Heitz, F.
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Hogdall, E.
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Bandera, E.V.
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Chang-Claude, J.
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Kupryjanczyk, J.
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Wentzensen, N.
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Lambrechts, D.
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Karlan, B.Y.
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Whittemore, A.S.
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Culver, H.A.
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Gronwald, J.
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Levine, D.A.
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Kjaer, S.K.
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Menon, U.
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Schildkraut, J.M.
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Pearce, C.L.
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Cramer, D.W.
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Rossing, M.A.
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Chenevix-Trench, G.
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Pharoah, P.D.P.
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Gayther, S.A.
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Ness, R.B.
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Odunsi, K.
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Sucheston, L.E.
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Knutson, K.L.
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Goode, E.L.
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Charbonneau, B.
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Moysich, K.B.
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Kalli, K.R.
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Oberg, A.L.
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Vierkant, R.A.
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Fogarty, Z.C.
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Block, M.S.
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Maurer, M.J.
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Goergen, K.M.
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Fridley, B.L.
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Cunningham, J.M.
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Rider, D.N.
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Preston, C.
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Hartmann, L.C.
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Lawrenson, K.
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Wang, C.
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Tyrer, J.
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Song, H.
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deFazio, A.
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Johnatty, S.E.
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Doherty, J.A.
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Phelan, C.M.
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Sellers, T.A.
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Ramirez, S.M.
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Vitonis, A.F.
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Terry, K.L.
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Van Den Berg, D.
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Pike, M.C.
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Wu, A.H.
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Berchuck, A.
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Gentry-Maharaj, A.
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Ramus, S.J.
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Diergaarde, B.
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Shen, H.
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Jensen, A.
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Menkiszak, J.
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Cybulski, C.
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Lubi ski, J.
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Ziogas, A.
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Rothstein, J.H.
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McGuire, V.
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Sieh, W.
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Lester, J.
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Walsh, C.
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Vergote, I.
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Lambrechts, S.
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Despierre, E.
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Garcia-Closas, M.
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Yang, H.
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Brinton, L.A.
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Spiewankiewicz, B.
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Rzepecka, I.K.
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Dansonka-Mieszkowska, A.
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Seibold, P.
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Rudolph, A.
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Paddock, L.E.
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Orlow, I.
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Lundvall, L.
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Olson, S.H.
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Hogdall, C.K.
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Schwaab, I.
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du Bois, A.
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Harter, P.
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Flanagan, J.M.
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Brown, R.
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Paul, J.
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Ekici, A.B.
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Beckmann, M.W.
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Hein, A.
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Eccles, D.
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Lurie, G.
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Hays, L.E.
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Bean, Y.T.
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Pejovic, T.
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Goodman, M.T.
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Campbell, I.
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Fasching, P.A.
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Konecny, G.
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Kaye, S.B.
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Heitz, F.
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Hogdall, E.
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Bandera, E.V.
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Chang-Claude, J.
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Kupryjanczyk, J.
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Wentzensen, N.
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Lambrechts, D.
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Karlan, B.Y.
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Whittemore, A.S.
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Culver, H.A.
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Gronwald, J.
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Levine, D.A.
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Kjaer, S.K.
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Menon, U.
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Schildkraut, J.M.
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Pearce, C.L.
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Cramer, D.W.
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Rossing, M.A.
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Chenevix-Trench, G.
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Pharoah, P.D.P.
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Gayther, S.A.
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Ness, R.B.
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Odunsi, K.
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Sucheston, L.E.
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Knutson, K.L.
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Goode, E.L.
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Charbonneau, B., Moysich, K.B. and Kalli, K.R. et al. (2014) Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome. Cancer Immunology Research, 2 (4), 332-340. (doi:10.1158/2326-6066.CIR-13-0136). (PMID:24764580)

Record type: Article

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

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Accepted/In Press date: 20 December 2013
e-pub ahead of print date: 27 January 2014
Published date: 2014
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 382772
URI: http://eprints.soton.ac.uk/id/eprint/382772
DOI: doi:10.1158/2326-6066.CIR-13-0136
ISSN: 2326-6066
PURE UUID: 657a1bd7-2e2c-4750-acc1-2bfcf13e24a2
ORCID for D. Eccles: ORCID iD orcid.org/0000-0002-9935-3169

Catalogue record

Date deposited: 12 Oct 2015 12:01
Last modified: 15 Mar 2024 02:40

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Contributors

Author: B. Charbonneau
Author: K.B. Moysich
Author: K.R. Kalli
Author: A.L. Oberg
Author: R.A. Vierkant
Author: Z.C. Fogarty
Author: M.S. Block
Author: M.J. Maurer
Author: K.M. Goergen
Author: B.L. Fridley
Author: J.M. Cunningham
Author: D.N. Rider
Author: C. Preston
Author: L.C. Hartmann
Author: K. Lawrenson
Author: C. Wang
Author: J. Tyrer
Author: H. Song
Author: A. deFazio
Author: S.E. Johnatty
Author: J.A. Doherty
Author: C.M. Phelan
Author: T.A. Sellers
Author: S.M. Ramirez
Author: A.F. Vitonis
Author: K.L. Terry
Author: D. Van Den Berg
Author: M.C. Pike
Author: A.H. Wu
Author: A. Berchuck
Author: A. Gentry-Maharaj
Author: S.J. Ramus
Author: B. Diergaarde
Author: H. Shen
Author: A. Jensen
Author: J. Menkiszak
Author: C. Cybulski
Author: J. Lubi ski
Author: A. Ziogas
Author: J.H. Rothstein
Author: V. McGuire
Author: W. Sieh
Author: J. Lester
Author: C. Walsh
Author: I. Vergote
Author: S. Lambrechts
Author: E. Despierre
Author: M. Garcia-Closas
Author: H. Yang
Author: L.A. Brinton
Author: B. Spiewankiewicz
Author: I.K. Rzepecka
Author: A. Dansonka-Mieszkowska
Author: P. Seibold
Author: A. Rudolph
Author: L.E. Paddock
Author: I. Orlow
Author: L. Lundvall
Author: S.H. Olson
Author: C.K. Hogdall
Author: I. Schwaab
Author: A. du Bois
Author: P. Harter
Author: J.M. Flanagan
Author: R. Brown
Author: J. Paul
Author: A.B. Ekici
Author: M.W. Beckmann
Author: A. Hein
Author: D. Eccles ORCID iD
Author: G. Lurie
Author: L.E. Hays
Author: Y.T. Bean
Author: T. Pejovic
Author: M.T. Goodman
Author: I. Campbell
Author: P.A. Fasching
Author: G. Konecny
Author: S.B. Kaye
Author: F. Heitz
Author: E. Hogdall
Author: E.V. Bandera
Author: J. Chang-Claude
Author: J. Kupryjanczyk
Author: N. Wentzensen
Author: D. Lambrechts
Author: B.Y. Karlan
Author: A.S. Whittemore
Author: H.A. Culver
Author: J. Gronwald
Author: D.A. Levine
Author: S.K. Kjaer
Author: U. Menon
Author: J.M. Schildkraut
Author: C.L. Pearce
Author: D.W. Cramer
Author: M.A. Rossing
Author: G. Chenevix-Trench
Author: P.D.P. Pharoah
Author: S.A. Gayther
Author: R.B. Ness
Author: K. Odunsi
Author: L.E. Sucheston
Author: K.L. Knutson
Author: E.L. Goode

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