2024-03-29T09:59:48Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/110752022-10-06T08:38:40Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2174com_20.500.12105_2173com_20.500.12105_2102com_20.500.12105_2052col_20.500.12105_16968col_20.500.12105_2175col_20.500.12105_2103
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
Patino-Garcia, 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.
http://hdl.handle.net/20.500.12105/11075
32881892
10.1371/journal.pone.0237792
1932-6203
PloS one
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.
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).
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).
These findings suggest rare variation residing on common haplotypes are important contributors to EwS risk.
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.
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/11075/1/LowFrequencyVariationNear_2020.pdf
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https://repisalud.isciii.es/bitstream/20.500.12105/11075/6/LowFrequencyVariationNear_2020.pdf.txt
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LowFrequencyVariationNear_2020.pdf.txt