1. Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma
- Author
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Cuiping Hou, Sharon J. Diskin, Achille Iolascon, Maura Diamond, Jayanti Jagannathan, Mario Capasso, Robert W. Schnepp, Marcella Devoto, Hakon Hakonarson, Erica L. Carpenter, Valeria Latorre, Edward F. Attiyeh, Kristina A. Cole, Hanna Lee, John M. Maris, Cynthia Winter, S. J., Diskin, Capasso, Mario, R. W., Schnepp, K. A., Cole, E. F., Attiyeh, C., Hou, M., Diamond, E. L., Carpenter, C., Winter, H., Lee, J., Jagannathan, V., Latorre, Iolascon, Achille, H., Hakonarson, M., Devoto, and J. M. M. a. r. i., S.
- 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 - 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.
- Published
- 2012