| Autor: |
Ellen L. Goode, Brooke L. Fridley, Julie M. Cunningham, Keith L. Knutson, Kirsten Moysich, Paul D.P. Pharoah, Linda E. Kelemen, Piotr Sobiczewski, Michelle A.T. Hildebrandt, Montserrat Garcia-Closas, Ignace Vergote, Joseph H. Rothstein, Grace Friel, Francesmary Modugno, Arto Leminen, Lynne R. Wilkens, Arif B. Ekici, Janusz Menkiszak, Urmila Chandran, Ira Schwaab, Aleksandra Gentry-Maharaj, Mari K. Halle, David van den Berg, Anne M. Van Altena, Liisa M. Pelttari, Matthias W. Beckmann, Hannah Yang, Sandrina Lambrechts, Lukasz M. Szafron, Shan Wang-Gohrke, Lene Lundvall, Andreas du Bois, Jenny Lester, Valerie McGuire, Robert Edwards, Lara Sucheston, Jie Lin, Cezary Cybulski, Elisabeth Wik, Susan J. Ramus, Malcolm C. Pike, Katja K. Aben, Angela Brooks-Wilson, Allison F. Vitonis, Jonathan Tyrer, Philipp Harter, Sara H. Olson, Agnieszka Dansonka-Mieszkowska, Anja Rudolph, Alexander Hein, Louise Brinton, Evelyn Despierre, Christine Walsh, Argyrios Ziogas, Galina Lurie, Yukie T. Bean, Heli Nevanlinna, Jan Lubiński, Allan Jensen, Andrew Berchuck, Kunle Odunsi, Dong Liang, Camilla Krakstad, Jennifer A. Doherty, Honglin Song, Leon F.A.G. Massuger, Robert Brown, Catherine M. Phelan, James M. Flanagan, Daniel Cramer, Susanne Kruger Kjaer, Douglas A. Levine, Celeste Leigh Pearce, Joellen Schildkraut, Usha Menon, Peter A. Fasching, Diether Lambrechts, Claus K. Hogdall, Jacek Gronwald, Hoda Anton-Culver, Beth Y. Karlan, Stanley B. Kaye, Florian Heitz, Estrid Hogdall, Simon A. Gayther, Anna H. Wu, James Paul, Diana Eccles, Ingo B. Runnebaum, Natalia Bogdanova, Clareann H. Bunker, Nhu D. Le, Ian Campbell, Tanja Pejovic, Thilo Dörk, Ralf Butzow, Karen Lu, Jolanta Kupryjanczyk, Steven A. Narod, Roberta B. Ness, Mary Anne Rossing, Linda S. Cook, Pamela J. Thompson, Marc T. Goodman, Kathryn Terry, Irene Orlow, Elisa V. Bandera, Jenny Chang-Claude, Weiva Sieh, Alice S. Whittemore, Georgia Chenevix-Trench, Nicolas Wentzensen, Britton Trabert, Gianluca Severi, Graham G. Giles, Laura Baglietto, Lambertus A. Kiemeney, Helga B. Salvesen, Harvey A. Risch, Elizabeth Poole, Shelley S. Tworoger, Thomas A. Sellers, David N. Rider, Zachary Fogarty, Kimberly R. Kalli, Robert A. Vierkant, William R. Bamlet, Matthew S. Block, Bridget Charbonneau |
| Rok vydání: |
2023 |
| DOI: |
10.1158/0008-5472.c.6505940 |
| Popis: |
A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1α (IL1A) is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76–0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75–0.95; P = 0.006). Considering a multiple-testing–corrected significance threshold of P < 2.5 × 10−5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79–0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted. Cancer Res; 74(3); 852–61. ©2013 AACR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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