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

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133 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 1 2013

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ASJC Scopus subject areas

  • Genetics

Cite this

Savage, S. A., Mirabello, L., Wang, Z., Gastier-Foster, J. M., Gorlick, R., Khanna, C., Flanagan, A. M., Tirabosco, R., Andrulis, I. L., Wunder, J. S., Gokgoz, N., Patiño-Garcia, A., Sierrasesúmaga, L., Lecanda, F., Kurucu, N., Ilhan, I. E., Sari, N., Serra, M., Hattinger, C., ... Chanock, S. J. (2013). Genome-wide association study identifies two susceptibility loci for osteosarcoma. Nature Genetics, 45(7), 799-803. https://doi.org/10.1038/ng.2645