Prostate Cancer Risk Variant at 8q24 Linked to PVT1 Expression
Author Information
Author(s): Kerstin B. Meyer, Ana-Teresa Maia, Martin O'Reilly, Maya Ghoussaini, Radhika Prathalingam, Patricia Porter-Gill, Stefan Ambs, Ludmila Prokunina-Olsson, Jason Carroll, Bruce A. J. Ponder
Primary Institution: Cancer Research UK Cambridge Research Institute, University of Cambridge, National Cancer Institute, National Institutes of Health
Hypothesis
Can regulatory elements affected by SNPs in the 8q24 region influence prostate cancer susceptibility?
Conclusion
The study identifies a new functional prostate cancer risk variant at the 8q24 locus that reduces YY1 protein binding and is associated with increased expression of the PVT1 oncogene.
Supporting Evidence
- Genome-wide association studies have identified multiple cancer susceptibility regions at chromosome 8q24.
- The risk allele of rs378854 reduces binding of the transcription factor YY1 in vitro.
- Expression of the PVT1 oncogene in normal prostate tissue increased with the presence of the risk allele of rs378854.
- YY1 binding site is occupied in vivo in prostate cancer but not breast cancer cells.
- Chromatin conformation capture experiments showed that the region surrounding rs378854 interacts with the MYC and PVT1 promoters.
Takeaway
Scientists found a genetic change that can make people more likely to get prostate cancer by affecting how a gene called PVT1 works.
Methodology
The study used DNase I hypersensitive site mapping, chromatin conformation capture, and expression analysis in prostate tissue samples.
Limitations
The study's findings need to be validated in larger sample sizes and different populations.
Participant Demographics
The study included normal prostate tissue samples from individuals of European-American and African-American descent.
Statistical Information
P-Value
0.025
Statistical Significance
p=0.025
Digital Object Identifier (DOI)
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