Benutzer: Gast  Login
Titel:

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

Dokumenttyp:
Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't
Autor(en):
Lin, Shu-Hong; Sampson, Joshua N; Grünewald, Thomas G P; Surdez, Didier; Reynaud, Stephanie; Mirabeau, Olivier; Karlins, Eric; Rubio, Rebeca Alba; Zaidi, Sakina; Grossetête-Lalami, Sandrine; Ballet, Stelly; Lapouble, Eve; Laurence, Valérie; Michon, Jean; Pierron, Gaelle; Kovar, Heinrich; Kontny, Udo; González-Neira, Anna; Alonso, Javier; Patino-Garcia, Ana; Corradini, Nadège; Bérard, Perrine Marec; Miller, Jeremy; Freedman, Neal D; Rothman, Nathaniel; Carter, Brian D; Dagnall, Casey L; Burdett,...     »
Abstract:
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.
Zeitschriftentitel:
PLoS ONE
Jahr:
2020
Band / Volume:
15
Heft / Issue:
9
Volltext / DOI:
doi:10.1371/journal.pone.0237792
PubMed:
http://view.ncbi.nlm.nih.gov/pubmed/32881892
Print-ISSN:
1932-6203
TUM Einrichtung:
656; 658; Institut für Humangenetik
 BibTeX