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Association analyses identify 31 new risk loci for colorectal cancer susceptibility.

ABSTRACT: 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.

SUBMITTER: Law PJ 

PROVIDER: S-EPMC6517433 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Association analyses identify 31 new risk loci for colorectal cancer susceptibility.

Law Philip J PJ   Timofeeva Maria M   Fernandez-Rozadilla Ceres C   Broderick Peter P   Studd James J   Fernandez-Tajes Juan J   Farrington Susan S   Svinti Victoria V   Palles Claire C   Orlando Giulia G   Sud Amit A   Holroyd Amy A   Penegar Steven S   Theodoratou Evropi E   Vaughan-Shaw Peter P   Campbell Harry H   Zgaga Lina L   Hayward Caroline C   Campbell Archie A   Harris Sarah S   Deary Ian J IJ   Starr John J   Gatcombe Laura L   Pinna Maria M   Briggs Sarah S   Martin Lynn L   Jaeger Emma E   Sharma-Oates Archana A   East James J   Leedham Simon S   Arnold Roland R   Johnstone Elaine E   Wang Haitao H   Kerr David D   Kerr Rachel R   Maughan Tim T   Kaplan Richard R   Al-Tassan Nada N   Palin Kimmo K   Hänninen Ulrika A UA   Cajuso Tatiana T   Tanskanen Tomas T   Kondelin Johanna J   Kaasinen Eevi E   Sarin Antti-Pekka AP   Eriksson Johan G JG   Rissanen Harri H   Knekt Paul P   Pukkala Eero E   Jousilahti Pekka P   Salomaa Veikko V   Ripatti Samuli S   Palotie Aarno A   Renkonen-Sinisalo Laura L   Lepistö Anna A   Böhm Jan J   Mecklin Jukka-Pekka JP   Buchanan Daniel D DD   Win Aung-Ko AK   Hopper John J   Jenkins Mark E ME   Lindor Noralane M NM   Newcomb Polly A PA   Gallinger Steven S   Duggan David D   Casey Graham G   Hoffmann Per P   Nöthen Markus M MM   Jöckel Karl-Heinz KH   Easton Douglas F DF   Pharoah Paul D P PDP   Peto Julian J   Canzian Federico F   Swerdlow Anthony A   Eeles Rosalind A RA   Kote-Jarai Zsofia Z   Muir Kenneth K   Pashayan Nora N   Harkin Andrea A   Allan Karen K   McQueen John J   Paul James J   Iveson Timothy T   Saunders Mark M   Butterbach Katja K   Chang-Claude Jenny J   Hoffmeister Michael M   Brenner Hermann H   Kirac Iva I   Matošević Petar P   Hofer Philipp P   Brezina Stefanie S   Gsur Andrea A   Cheadle Jeremy P JP   Aaltonen Lauri A LA   Tomlinson Ian I   Houlston Richard S RS   Dunlop Malcolm G MG  

Nature communications 20190514 1

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 e  ...[more]

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