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Association analyses identify 31 new risk loci for colorectal cancer susceptibility
Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England.
Univ Edinburgh, Western Gen Hosp, Med Res Council Human Genet Unit, Insti Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.ORCID iD: 0000-0002-2503-4253
Inst Invest Santiago, Fdn Publ Galega Med Xenom, Grp Med Xenom, Santiago De Compostela 15706, Spain;Univ Birmingham, Inst Canc & Genom Sci, Canc Genet & Evolut Lab, Vincent Dr, Birmingham B15 2TT, W Midlands, England.
Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England.
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2019 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, article id 2154Article in journal (Refereed) Published
Abstract [en]

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.

Place, publisher, year, edition, pages
2019. Vol. 10, article id 2154
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Medical Genetics Cancer and Oncology
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URN: urn:nbn:se:uu:diva-387286DOI: 10.1038/s41467-019-09775-wISI: 000467836900008PubMedID: 31089142OAI: oai:DiVA.org:uu-387286DiVA, id: diva2:1329243
Funder
EU, FP7, Seventh Framework Programme, 258236EU, FP7, Seventh Framework ProgrammeEU, European Research Council, 268648EU, FP7, Seventh Framework Programme, 201413EU, FP7, Seventh Framework Programme, 223175 (HEALTH-F2-2009-223175)Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-06-24Bibliographically approved

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