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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.

Original publication

DOI

10.1038/s41467-019-09775-w

Type

Journal article

Journal

Nature communications

Publication Date

14/05/2019

Volume

10

Addresses

Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.

Keywords

PRACTICAL consortium, Humans, Colorectal Neoplasms, Genetic Predisposition to Disease, Risk Factors, Case-Control Studies, Inheritance Patterns, Polymorphism, Single Nucleotide, Middle Aged, Asian Continental Ancestry Group, European Continental Ancestry Group, Female, Male, Genome-Wide Association Study, Genetic Loci, Datasets as Topic