Association analyses identify 31 new risk loci for colorectal cancer susceptibility
Law PJ., Timofeeva M., Fernandez-Rozadilla C., Broderick P., Studd J., Fernandez-Tajes J., Farrington S., Svinti V., Palles C., Orlando G., Sud A., Holroyd A., Penegar S., Theodoratou E., Vaughan-Shaw P., Campbell H., Zgaga L., Hayward C., Campbell A., Harris S., Deary IJ., Starr J., Gatcombe L., Pinna M., Briggs S., Martin L., Jaeger E., Sharma-Oates A., East J., Leedham S., Arnold R., Johnstone E., Wang H., Kerr D., Kerr R., Maughan T., Kaplan R., Al-Tassan N., Palin K., Hänninen UA., Cajuso T., Tanskanen T., Kondelin J., Kaasinen E., Sarin A-P., Eriksson JG., Rissanen H., Knekt P., Pukkala E., Jousilahti P., Salomaa V., Ripatti S., Palotie A., Renkonen-Sinisalo L., Lepistö A., Böhm J., Mecklin J-P., Buchanan DD., Win A-K., Hopper J., Jenkins ME., Lindor NM., Newcomb PA., Gallinger S., Duggan D., Casey G., Hoffmann P., Nöthen MM., Jöckel K-H., Easton DF., Pharoah PDP., Peto J., Canzian F., Swerdlow A., Eeles RA., Kote-Jarai Z., Muir K., Pashayan N., Henderson BE., Haiman CA., Schumacher FR., Al Olama AA., Benlloch S., Berndt SI., Conti DV., Wiklund F., Chanock S., Gapstur S., Stevens VL., Tangen CM., Batra J., Clements J., Gronberg H., Schleutker J., Albanes D., Wolk A., West C., Mucci L., Cancel-Tassin G., Koutros S., Sorensen KD., Grindedal EM., Neal DE., Hamdy FC., Donovan JL., Travis RC., Hamilton RJ., Ingles SA., Rosenstein BS., Lu Y-J., Giles GG., Kibel AS., Vega A., Kogevinas M., Penney KL., Park JY., Stanford JL., Cybulski C., Nordestgaard BG., Maier C., Kim J., John EM., Teixeira MR., Neuhausen SL., De Ruyck K., Razack A., Newcomb LF., Gamulin M., Kaneva R., Usmani N., Claessens F., Townsend PA., Gago-Dominguez M., Roobol MJ., Menegaux F., Khaw K-T., Cannon-Albright L., Pandha H., Thibodeau SN., Harkin A., Allan K., McQueen J., Paul J., Iveson T., Saunders M., Butterbach K., Chang-Claude J., Hoffmeister M., Brenner H., Kirac I., Matošević P., Hofer P., Brezina S., Gsur A., Cheadle JP., Aaltonen LA., Tomlinson I., Houlston RS., Dunlop MG.
AbstractColorectal 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.