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oai:repisalud.isciii.es:20.500.12105/110752025-05-05T14:51:52Zcom_20.500.12105_2173com_20.500.12105_2051com_20.500.12105_15322com_20.500.12105_2052col_20.500.12105_19597col_20.500.12105_16968col_20.500.12105_19616
Repisalud author Lin, Shu-Hong author Sampson, Joshua N author Grünewald, Thomas G P author Surdez, Didier author Reynaud, Stephanie author Mirabeau, Olivier author Karlins, Eric author Rubio, Rebeca Alba author Zaidi, Sakina author Grossetête-Lalami, Sandrine author Ballet, Stelly author Lapouble, Eve author Laurence, Valérie author Michon, Jean author Pierron, Gaelle author Kovar, Heinrich author Kontny, Udo author González-Neira, Anna author Alonso, Javier author Patiño-García, Ana author Corradini, Nadège author Bérard, Perrine Marec author Miller, Jeremy author Freedman, Neal D author Rothman, Nathaniel author Carter, Brian D author Dagnall, Casey L author Burdett, Laurie author Jones, Kristine author Manning, Michelle author Wyatt, Kathleen author Zhou, Weiyin author Yeager, Meredith author Cox, David G author Hoover, Robert N author Khan, Javed author Armstrong, Gregory T author Leisenring, Wendy M author Bhatia, Smita author Robison, Leslie L author Kulozik, Andreas E author Kriebel, Jennifer author Meitinger, Thomas author Metzler, Markus author Krumbholz, Manuela author Hartmann, Wolfgang author Strauch, Konstantin author Kirchner, Thomas author Dirksen, Uta author Mirabello, Lisa author Tirode, Franck author Tucker, Margaret A author Morton, Lindsay M author Chanock, Stephen J author Delattre, Olivier author Machiela, Mitchell J funder NIH - National Cancer Institute (NCI) (Estados Unidos) funder Agence Nationale de la Recherche (Francia) funder Unión Europea. Comisión Europea. 7 Programa Marco funder Deutsche Forschungsgemeinschaft (Alemania) funder Instituto de Salud Carlos III funder Comunidad Foral de Navarra (España) 2020-09-24T18:52:15Z 2020-09-24T18:52:15Z 2020 PLoS One . 2020 Sep 3;15(9):e0237792. 10.1371/journal.pone.0237792 1932-6203 PloS one 32881892 http://hdl.handle.net/20.500.12105/11075 Background: Ewing sarcoma (EwS) is a rare, aggressive solid tumor of childhood, adolescence and young adulthood associated with pathognomonic EWSR1-ETS fusion oncoproteins altering transcriptional regulation. Genome-wide association studies (GWAS) have identified 6 common germline susceptibility loci but have not investigated low-frequency inherited variants with minor allele frequencies below 5% due to limited genotyped cases of this rare tumor. Methods: We investigated the contribution of rare and low-frequency variation to EwS susceptibility in the largest EwS genome-wide association study to date (733 EwS cases and 1,346 unaffected controls of European ancestry). Results: We identified two low-frequency variants, rs112837127 and rs2296730, on chromosome 20 that were associated with EwS risk (OR = 0.186 and 2.038, respectively; P-value < 5×10-8) and located near previously reported common susceptibility loci. After adjusting for the most associated common variant at the locus, only rs112837127 remained a statistically significant independent signal (OR = 0.200, P-value = 5.84×10-8). Conclusions: These findings suggest rare variation residing on common haplotypes are important contributors to EwS risk. Impact: Motivate future targeted sequencing studies for a comprehensive evaluation of low-frequency and rare variation around common EwS susceptibility loci. eng Low-frequency variation near common germline susceptibility loci are associated with risk of Ewing sarcoma research article 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 URL https://repisalud.isciii.es/bitstreams/fdb47471-bfe9-4794-aef0-5197533a6af9/download File MD5 5b2cbbc005638a4e5b4121b554ecdd91 987820 application/pdf LowFrequencyVariationNear_2020.pdf URL https://repisalud.isciii.es/bitstreams/a687a42d-77d9-4450-abc7-44eb329325a4/download File MD5 f2277aa8cd0c184b76687e1841ee4d56 45191 text/plain LowFrequencyVariationNear_2020.pdf.txt