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PLoS One. 2015 Mar 24;10(3):e0116477. doi: 10.1371/journal.pone.0116477. eCollection 2015.

Use of genome-wide association studies for cancer research and drug repositioning.

Author information

1
Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, PR China.
2
Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, PR China.

Abstract

Although genome-wide association studies have identified many risk loci associated with colorectal cancer, the molecular basis of these associations are still unclear. We aimed to infer biological insights and highlight candidate genes of interest within GWAS risk loci. We used an in silico pipeline based on functional annotation, quantitative trait loci mapping of cis-acting gene, PubMed text-mining, protein-protein interaction studies, genetic overlaps with cancer somatic mutations and knockout mouse phenotypes, and functional enrichment analysis to prioritize the candidate genes at the colorectal cancer risk loci. Based on these analyses, we observed that these genes were the targets of approved therapies for colorectal cancer, and suggested that drugs approved for other indications may be repurposed for the treatment of colorectal cancer. This study highlights the use of publicly available data as a cost effective solution to derive biological insights, and provides an empirical evidence that the molecular basis of colorectal cancer can provide important leads for the discovery of new drugs.

PMID:
25803826
PMCID:
PMC4372357
DOI:
10.1371/journal.pone.0116477
[Indexed for MEDLINE]
Free PMC Article

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