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

Abstract：

: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.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Koster R,Panagiotou OA,Wheeler WA,Karlins E,Gastier-Foster JM,Caminada de Toledo SR,Petrilli AS,Flanagan AM,Tirabosco R,Andrulis IL,Wunder JS,Gokgoz N,Patiño-Garcia A,Lecanda F,Serra M,Hattinger C,Picci P,Scotlandi K,

doi

10.1002/ijc.31195

subject

Has Abstract

pub_date

2018-04-15 00:00:00

pages

1594-1601

issue

eissn

0020-7136

issn

1097-0215

journal_volume

142

pub_type

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