Genome-wide association study identifies the GLDC/IL33 locus associated with survival of osteosarcoma patients.

Autor: Koster R; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD., Panagiotou OA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD., Wheeler WA; Information Management Services (IMS), Inc. Rockville, MD., Karlins E; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD., Gastier-Foster JM; The Ohio State University Department of Pathology and Pediatrics, Nationwide Children's Hospital, Columbus, OH., Caminada de Toledo SR; Laboratorio de Genética, Pediatric Oncology Institute, GRAACC/UNIFESP, São Paulo, Brazil., Petrilli AS; Laboratorio de Genética, Pediatric Oncology Institute, GRAACC/UNIFESP, São Paulo, Brazil., Flanagan AM; UCL Cancer Institute, Huntley Street, London, United Kingdom.; Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, United Kingdom., Tirabosco R; Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, United Kingdom., Andrulis IL; Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada., Wunder JS; Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada., Gokgoz N; Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada., Patiño-Garcia A; Department of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain., Lecanda F; Department of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain., Serra M; Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy., Hattinger C; Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy., Picci P; Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy., Scotlandi K; Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy., Thomas DM; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia., Ballinger ML; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia., Gorlick R; Department of Pediatrics, University of Texas, MD Anderson Cancer Center, Houston, Texas, US., Barkauskas DA; Keck School of Medicine, University of Southern California, Los Angeles, CA., Spector LG; Department of Pediatrics, University of Minnesota Minneapolis, MN., Tucker M; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD., Belynda DH; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD., Yeager M; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD., Hoover RN; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD., Wacholder S; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD., Chanock SJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD., Savage SA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD., Mirabello L; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2018 Apr 15; Vol. 142 (8), pp. 1594-1601. Date of Electronic Publication: 2017 Dec 23.
DOI: 10.1002/ijc.31195
Abstrakt: Survival rates for osteosarcoma, the most common primary bone cancer, have changed little over the past three decades and are particularly low for patients with metastatic disease. We conducted a multi-institutional genome-wide association study (GWAS) to identify germline genetic variants associated with overall survival in 632 patients with osteosarcoma, including 523 patients of European ancestry and 109 from Brazil. We conducted a time-to-event analysis and estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models, with and without adjustment for metastatic disease. The results were combined across the European and Brazilian case sets using a random-effects meta-analysis. The strongest association after meta-analysis was for rs3765555 at 9p24.1, which was inversely associated with overall survival (HR = 1.76; 95% CI 1.41-2.18, p = 4.84 × 10 -7 ). After imputation across this region, the combined analysis identified two SNPs that reached genome-wide significance. The strongest single association was with rs55933544 (HR = 1.9; 95% CI 1.5-2.4; p = 1.3 × 10 -8 ), which localizes to the GLDC gene, adjacent to the IL33 gene and was consistent across both the European and Brazilian case sets. Using publicly available data, the risk allele was associated with lower expression of IL33 and low expression of IL33 was associated with poor survival in an independent set of patients with osteosarcoma. In conclusion, we have identified the GLDC/IL33 locus on chromosome 9p24.1 as associated with overall survival in patients with osteosarcoma. Further studies are needed to confirm this association and shed light on the biological underpinnings of this susceptibility locus.
(© 2017 UICC.)
Databáze: MEDLINE
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