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Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma
- Source :
- Nature genetics
- Publication Year :
- 2012
- Publisher :
- NATURE PUBLISHING GROUP, 2012.
-
Abstract
- Neuroblastoma is a cancer of the sympathetic nervous system that accounts for approximately 10% of all pediatric oncology deaths. Here, we report a genome-wide association study of 2,817 neuroblastoma cases and 7,473 controls. We identified two new associations at 6q16, the first within HACE1 (rs4336470; combined P=2.7×10(-11); odds ratio 1.26, 95% confidence interval (CI) 1.18-1.35) and the second within LIN28B (rs17065417; combined P=1.2×10(-8); odds ratio 1.38, 95% CI 1.23-1.54). Expression of LIN28B and let-7 miRNA correlated with rs17065417 genotype in neuroblastoma cell lines, and we observed significant growth inhibition upon depletion of LIN28B, specifically in neuroblastoma cells that were homozygous for the risk allele. Low HACE1 and high LIN28B expression in diagnostic primary neuroblastomas were associated with worse overall survival (P=0.008 and 0.014, respectively). Taken together, these data show that common variants in HACE1 and LIN28B influence neuroblastoma susceptibility and indicate that both genes likely have a role in disease progression.
- Subjects :
- Linkage disequilibrium
Ubiquitin-Protein Ligases
Gene Expression
Genome-wide association study
Kaplan-Meier Estimate
Biology
Polymorphism, Single Nucleotide
Linkage Disequilibrium
Article
Transcriptome
Cohort Studies
03 medical and health sciences
neuroblastoma
0302 clinical medicine
Gene Frequency
Neuroblastoma
Cell Line, Tumor
Genetics
medicine
Humans
Genetic Predisposition to Disease
neoplasms
Gene
Allele frequency
030304 developmental biology
Cell Proliferation
Oligonucleotide Array Sequence Analysis
0303 health sciences
Case-control study
Infant
RNA-Binding Proteins
Sequence Analysis, DNA
medicine.disease
3. Good health
DNA-Binding Proteins
030220 oncology & carcinogenesis
Case-Control Studies
Gene Knockdown Techniques
Chromosomes, Human, Pair 6
RNA Interference
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Nature genetics
- Accession number :
- edsair.doi.dedup.....0edb25f8f79bfb3446bcd126c53cabbf