Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome
| العنوان: | Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome |
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| المؤلفون: | Weiva Sieh, Anna H. Wu, Tanja Pejovic, Florian Heitz, Beth Y. Karlan, David Van Den Berg, Joellen M. Schildkraut, Kimberly R. Kalli, Gottfried E. Konecny, Argyrios Ziogas, Usha Menon, Montserrat Garcia-Closas, Anja Rudolph, Jonathan Tyrer, Ann L. Oberg, Alice S. Whittemore, Brooke L. Fridley, Kunle Odunsi, Mary Anne Rossing, Beata Spiewankiewicz, Douglas A. Levine, Jennifer A. Doherty, Peter A. Fasching, Janusz Menkiszak, Matthew J. Maurer, Claus Høgdall, Zachary C. Fogarty, Louise A. Brinton, Galina Lurie, Diether Lambrechts, Allison F. Vitonis, Keith L. Knutson, Diana Eccles, Agnieszka Dansonka-Mieszkowska, Marc T. Goodman, Jenny Lester, Jolanta Kupryjanczyk, Nicolas Wentzensen, Celeste Leigh Pearce, Howard C. Shen, Simon A. Gayther, Kathryn L. Terry, Ira Schwaab, Bridget Charbonneau, Claudia C. Preston, Jan Lubinski, Krista M. Goergen, Georgia Chenevix-Trench, Susanne K. Kjaer, Irene Orlow, Sara H. Olson, Stanley B. Kaye, Matthias W. Beckmann, Daniel W. Cramer, Kate Lawrenson, Matthew S. Block, Paul D.P. Pharoah, Robert A. Vierkant, Chen Wang, Yukie Bean, Laura E. Hays, Sandrina Lambrechts, Catherine M. Phelan, Hoda Anton Culver, Kirsten B. Moysich, Estrid Høgdall, Malcolm C. Pike, Iwona K. Rzepecka, Ignace Vergote, Lara Sucheston, Joseph H. Rothstein, David N. Rider, Christine Walsh, Starr M. Ramirez, Evelyn Despierre, Lene Lundvall, Arif B. Ekici, Cezary Cybulski, Valerie McGuire, Anna deFazio, Ian G. Campbell, Hannah P. Yang, Alexander Hein, Roberta B. Ness, James Paul, Elisa V. Bandera, Jacek Gronwald, Andrew Berchuck, Andreas du Bois, Aleksandra Gentry-Maharaj, Jenny Chang-Claude, Ellen L. Goode, Lisa E. Paddock, Lynn C. Hartmann, Sharon E. Johnatty, Philipp Harter, James M. Flanagan, Brenda Diergaarde, Julie M. Cunningham, Robert S. Brown, Allan Jensen, Thomas A. Sellers, Honglin Song, Susan J. Ramus, Petra Seibold |
| المصدر: | Cancer Immunology Research. 2:332-340 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Oncology, Cancer Research, medicine.medical_specialty, Immunology, Gene Expression, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, T-Lymphocytes, Regulatory, Article, Internal medicine, Genotype, medicine, Carcinoma, Humans, Mucinous carcinoma, Genetic Predisposition to Disease, Neoplasm Invasiveness, Germ-Line Mutation, Ovarian Neoplasms, Gene Expression Profiling, Interleukin-2 Receptor alpha Subunit, Genetic Variation, FOXP3, Prognosis, medicine.disease, Patient Outcome Assessment, Clear cell carcinoma, Female, Neoplasm Grading, Ovarian cancer, Clear cell |
| الوصف: | 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. Cancer Immunol Res; 2(4); 332–40. ©2014 AACR. |
| تدمد: | 2326-6074 2326-6066 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::35419f66709078c0619a3871d1745e30Test https://doi.org/10.1158/2326-6066.cir-13-0136Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....35419f66709078c0619a3871d1745e30 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23266074 23266066 |
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