Genome-wide association study identifies two susceptibility loci for osteosarcoma

Sharon A. Savage, Lisa Mirabello, Zhaoming Wang, Julie M. Gastier-Foster, Richard Gorlick, Chand Khanna, Adrienne M. Flanagan, Roberto Tirabosco, Irene L. Andrulis, Jay S. Wunder, Nalan Gokgoz, Ana Patiño-Garcia, Luis Sierrasesúmaga, Fernando Lecanda, Nilgün Kurucu, Inci Ergurhan Ilhan, Neriman Sari, Massimo Serra, Claudia Hattinger, Piero PicciLogan G. Spector, Donald A. Barkauskas, Neyssa Marina, Silvia Regina Caminada De Toledo, Antonio S. Petrilli, Maria Fernanda Amary, Dina Halai, David M. Thomas, Chester Douglass, Paul S. Meltzer, Kevin Jacobs, Charles C. Chung, Sonja I. Berndt, Mark P. Purdue, Neil E. Caporaso, Margaret Tucker, Nathaniel Rothman, Maria Teresa Landi, Debra T. Silverman, Peter Kraft, David J. Hunter, Nuria Malats, Manolis Kogevinas, Sholom Wacholder, Rebecca Troisi, Lee Helman, Joseph F. Fraumeni, Meredith Yeager, Robert N. Hoover, Stephen J. Chanock

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

Abstract

Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.3 (encoding glutamate receptor metabotropic 4; rs1906953; P = 8.1 × 10 -9) and a locus in the gene desert at 2p25.2 (rs7591996 and rs10208273; P = 1.0 × 10 -8 and 2.9 × 10 -7, respectively). These two loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma.

Original languageEnglish (US)
Pages (from-to)799-803
Number of pages5
JournalNature Genetics
Volume45
Issue number7
DOIs
StatePublished - Jul 2013

Bibliographical note

Funding Information:
We thank G. Maganoli for tissue banking, M. Fanelli for DNA isolation and C. Ferrari for updating clinicopathological data at the Orthopaedic Rizzoli Institute. We thank A. Griffin and D. Marsilio for data collection and T. Selander and the Biospecimen Repository staff at Mount Sinai Hospital. We acknowledge the advice of F. Real at the Spanish National Cancer Research Centre (CNIO). We thank F. Tesser Gamba at the Pediatric Oncology Institute at GRAACC-UNIFESP, and we also thank the International Sarcoma Kindred Study. This study was funded by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health and the Bone Cancer Research Trust UK. Research is supported by the Chair’s Grant U10 CA98543 and Human Specimen Banking Grant U24 CA114766 to the Children’s Oncology Group from the National Cancer Institute, US National Institutes of Health. Additional support for research is provided by a grant from the WWWW (QuadW) Foundation to the Children’s Oncology Group. This work was supported by grants to I.L.A. and J.S.W. from the Ontario Research Fund and Canadian Foundation for Innovation. This study was also supported by biobank grants from the Regione Emilia-Romagna and by the infrastructure and personnel of the Royal National Orthopaedic Hospital Musculoskeletal Research Programme and Biobank. Support was also provided to A.M.F. by the National Institute for Health Research UCL Hospitals (UCLH) Biomedical Research Centre and the UCL Experimental Cancer Centre. Funding was also provided by PI10/01580, the Fondo de Investigación Sanitaria (FIS), the Instituto de Salud Carlos III (ISCIII) and the Caja de Ahorros de Navarra (CAN) Programme ‘Tú eliges, tú decides’ to A.P.-G. and L.S. and by an Asociación Española Contra el Cáncer (AECC) project to F.L.

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