Low-frequency variation near common germline susceptibility loci are associated with risk of Ewing sarcoma - Centre Paul Strauss
Article Dans Une Revue PLoS ONE Année : 2020

Low-frequency variation near common germline susceptibility loci are associated with risk of Ewing sarcoma

1 NIH - National Institutes of Health [Bethesda, MD, USA]
2 KITZ - Hopp Children's Cancer Center Heidelberg [Heidelber, Germany]
3 DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
4 Heidelberg University Hospital [Heidelberg]
5 U830 - Unité de génétique et biologie des cancers
6 Institut Curie, PSL Research University, Radiation Oncology Department, Proton Therapy Centre
7 Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics
8 Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics
9 Laboratory for Pediatric Sarcoma Biology [Munich, Germany]
10 ICM - Institut du Cerveau = Paris Brain Institute
11 U830 - Unité de génétique et biologie des cancers
12 Institut Curie [Paris]
13 Département d'Oncologie Médicale [Institut Curie, Paris]
14 Unité de Génétique Somatique [Institut Curie, Paris]
15 PSL - Université Paris Sciences et Lettres
16 Children’s Cancer Research Institute [Vienna, Austria]
17 RWTH - Rheinisch-Westfälische Technische Hochschule Aachen University
18 CNIO - Spanish National Cancer Research Center
19 Unidad de Tumores Sólidos Infantiles – Unidad de Investigación Biomédica [Madrid, Spain]
20 CIMA - Center for Applied Medical Research [Plamplona]
21 CLB - Centre Régional de Lutte Contre le Cancer Lyon Rhône-Alpes
22 IHOPe - Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL]
23 Willamette University
24 Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis]
25 American Cancer Society [Atlanta, GA, USA]
26 FNLCR - Frederick National Laboratory for Cancer Research
27 NCI-NIH - National Cancer Institute [Bethesda]
28 IRFAC - Inserm U1113 - Interface de Recherche Fondamentale et Appliquée en Cancérologie
29 CUMC - Columbia University Medical Center
30 University of Glasgow
31 Department of Epidemiology and Cancer Control [Memphis, TN, USA]
32 Cancer Prevention and Clinical Statistics Program [Seattle, WA, USA]
33 Institute for Cancer Outcomes and Survivorship [Birmingham, AL, USA]
Shu-Hong Lin
Jeremy Miller
Javed Khan
  • Fonction : Auteur
Leslie Robison
  • Fonction : Auteur
Andreas Kulozik
  • Fonction : Auteur
Jennifer Kriebel
  • Fonction : Auteur
Thomas Meitinger
  • Fonction : Auteur
Markus Metzler
  • Fonction : Auteur
Manuela Krumbholz
  • Fonction : Auteur
Wolfgang Hartmann
  • Fonction : Auteur
Konstantin Strauch
  • Fonction : Auteur
Thomas Kirchner
  • Fonction : Auteur
Uta Dirksen
  • Fonction : Auteur
Lisa Mirabello
  • Fonction : Auteur
Margaret Tucker
  • Fonction : Auteur
Lindsay Morton
  • Fonction : Auteur
Stephen Chanock
  • Fonction : Auteur
Mitchell Machiela
  • Fonction : Auteur

Résumé

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.
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hal-04647594 , version 1 (15-07-2024)

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Shu-Hong Lin, Joshua Sampson, Thomas Grünewald, Didier Surdez, Stephanie Reynaud, et al.. Low-frequency variation near common germline susceptibility loci are associated with risk of Ewing sarcoma. PLoS ONE, 2020, 15 (9), pp.e0237792. ⟨10.1371/journal.pone.0237792⟩. ⟨hal-04647594⟩
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