Portal de Periódicos da CAPES

Association analyses identify 31 new risk loci for colorectal cancer susceptibility

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-09775-w

2041-1723

Philip Law, Maria Timofeeva, Ceres Fernández‐Rozadilla, Peter Broderick, James B. Studd, Juan Fernández‐Tajes, Susan M. Farrington, Victoria Svinti, Claire Palles, Giulia Orlando, Amit Sud, Amy Holroyd, Steven Penegar, Evropi Τheodoratou, P G Vaughan-Shaw, Harry Campbell, Lina Zgaga, Caroline Hayward, Archie Campbell, Sarah E. Harris, Ian J. Deary, John M. Starr, Laura Gatcombe, Claudia M.A. Pinna, Sarah Briggs, Lynn Martin, Emma Jaeger, Archana Sharma‐Oates, James E. East, Simon J. Leedham, Roland Arnold, Elaine Johnstone, Haitao Wang, David Kerr, Rachel Kerr, Tim Maughan, Richard Kaplan, Nada Al Tassan, Kimmo Palin, Ulrika A. Hänninen, Tatiana Cajuso, Tomas Tanskanen, Johanna Kondelin, Eevi Kaasinen, Antti‐Pekka Sarin, Johan G. Eriksson, Harri Rissanen, Paul Knekt, ­Eero Pukkala, Pekka Jousilahti, Veikko Salomaa, Samuli Ripatti, Aarno Palotie, Laura Renkonen‐Sinisalo, Anna Lepistö, J. Böhm, Jukka‐Pekka Mecklin, Daniel D. Buchanan, Aung Ko Win, John L. Hopper, Mark A. Jenkins, Noralane M. Lindor, Polly A. Newcomb, Steven Gallinger, David Duggan, Graham Casey, Per Hoffmann, Markus M. Nöthen, Karl‐Heinz Jöckel, Douglas F. Easton, Paul D.P. Pharoah, Julian Peto, Federico Canzian, Anthony J. Swerdlow, Rosalind A. Eeles, Zsofia Kote‐Jarai, Kenneth Muir, Nora Pashayan, Brian E. Henderson, Christopher A. Haiman, Fredrick R. Schumacher, Ali Amin Al Olama, Sara Benlloch, Sonja I. Berndt, David V. Conti, Fredrik Wiklund, Stephen J. Chanock, Susan M. Gapstur, Victoria L. Stevens, Catherine M. Tangen, Jyotsna Batra, Judith A. Clements, Henrik Grönberg, Johanna Schleutker, Demetrius Albanes, Alicja Wolk, Catharine West, Lorelei A. Mucci, Géraldine Cancel‐Tassin, Stella Koutros, Karina D. Sørensen, Eli Marie Grindedal, David E. Neal, Freddie C. Hamdy, Jenny Donovan, Ruth C. Travis, Robert J. Hamilton, Sue A. Ingles, Barry S. Rosenstein, Yong‐Jie Lu, Graham G. Giles, Adam S. Kibel, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Jong Y. Park, Janet L. Stanford, Cezary Cybulski, Børge G. Nordestgaard, Christiane Maier, Jeri Kim, Esther M. John, Manuel R. Teixeira, Susan L. Neuhausen, Kim De Ruyck, Azad Hassan Abdul Razack, Lisa F. Newcomb, Marija Gamulin, Radka Kaneva, Nawaid Usmani, Frank Claessens, Paul A. Townsend, Manuela Gago‐Dominguez, Monique J. Roobol, F. Ménégaux, Kay‐Tee Khaw, Lisa Cannon‐Albright, Hardev Pandha, Stephen N. Thibodeau, Andrea Harkin, Karen Allan, John McQueen, James Paul, Timothy Iveson, Mark Saunders, Katja Butterbach, Jenny Chang‐Claude, Michael Hoffmeister, Hermann Brenner, Iva Kirac, Petar Matošević, Philipp Hofer, Stefanie Brezina, Andrea Gsur, Jeremy P. Cheadle, Lauri A. Aaltonen, Ian Tomlinson, Richard S. Houlston, Malcolm G. Dunlop,

RNA modifications and cancer

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.