TY - JOUR
T1 - Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome
AU - OCS Group ACS
AU - Charbonneau, Bridget
AU - Moysich, Kirsten B.
AU - Kalli, Kimberly R.
AU - Oberg, Ann L.
AU - Vierkant, Robert A.
AU - Fogarty, Zachary C.
AU - Block, Matthew S.
AU - Maurer, Matthew J.
AU - Goergen, Krista M.
AU - Fridley, Brooke L.
AU - Cunningham, Julie M.
AU - Rider, David N.
AU - Preston, Claudia
AU - Hartmann, Lynn C.
AU - Lawrenson, Kate
AU - Wang, Chen
AU - Tyrer, Jonathan
AU - Song, Honglin
AU - De Fazio, Anna
AU - Johnatty, Sharon E.
AU - Doherty, Jennifer A.
AU - Phelan, Catherine M.
AU - Sellers, Thomas A.
AU - Ramirez, Starr M.
AU - Vitonis, Allison F.
AU - Terry, Kathryn L.
AU - Van Den Berg, David
AU - Pike, Malcolm C.
AU - Wu, Anna H.
AU - Berchuck, Andrew
AU - Gentry-Maharaj, Aleksandra
AU - Ramus, Susan J.
AU - Diergaarde, Brenda
AU - Shen, Howard
AU - Jensen, Allan
AU - Menkiszak, Janusz
AU - Cybulski, Cezary
AU - Lubinski, Jan
AU - Ziogas, Argyrios
AU - Rothstein, Joseph H.
AU - McGuire, Valerie
AU - Sieh, Weiva
AU - Lester, Jenny
AU - Walsh, Christine
AU - Vergote, Ignace
AU - Lambrechts, Sandrina
AU - Despierre, Evelyn
AU - Garcia-Closas, Montserrat
AU - Yang, Hannah
AU - Brinton, Louise A.
N1 - Publisher Copyright:
© 2014 American Association for Cancer Research.
PY - 2014/4
Y1 - 2014/4
N2 - 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 rs 10795763(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) 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.
AB - 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 rs 10795763(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) 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.
UR - http://www.scopus.com/inward/record.url?scp=84905051761&partnerID=8YFLogxK
U2 - 10.1158/2326-6066.CIR-13-0136
DO - 10.1158/2326-6066.CIR-13-0136
M3 - Article
C2 - 24764580
AN - SCOPUS:84905051761
SN - 2326-6066
VL - 2
SP - 332
EP - 340
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 4
ER -