Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease

Giulia Orlando, Philip J Law, Kimmo Palin, Sari Tuupanen, Alexandra Gylfe, Ulrika Hanninen, Tatiana Cajuso, Tomas Tanskanen, Johanna Kondelin, Eevi Kaasinen, Antti-Pekka Sarin, Jaakko Kaprio, Johan G. Eriksson, Harri Rissanen, Paul Knekt, Eero Pukkala, Pekka Jousilahti, Veikko Salomaa, Samuli Ripatti, Aarno PalotieHeikki J Jarvinen, Laura Renkonen-Sinisalo, Anna Lepisto, Jan Bohm, Jukka-Pekka Meklin, Nada A. Al-Tassan, Claire Palles, Lynn Martin, Ella Barclay, Albert Tenesa, Susan Farrington, Maria Timofeeva, Brian F. Meyer, Salma M. Wakil, Harry Campbell, Christopher G Smith, Shelley Idziaszczyk, Timothy S. Maughan, Richard Kaplan, Rachel Kerr, David Kerr, Daniel Buchanan, Aung Ko Win, John L Hopper, Mark C Jenkins, Noralane M. Lindor, Polly A Newcomb, Steve Gallinger, David Conti, Fred Schumacher, Graham Casey, Jussi Taipale, Jeremy P Cheadle, Malcolm Dunlop, Ian Tomlinson, Lauri A Aaltonen, Richard S Houlston

Research output: Contribution to journalArticlepeer-review


To identify new risk loci for colorectal cancer (CRC) we conducted a meta-analysis of seven genome-wide association studies (GWAS) with independent replication, totalling 13,656 CRC cases and 21,667 controls of European ancestry. The combined analysis identified a new risk association for CRC at 2q35 marked by rs992157 (P= 3.15 × 10-8, odds ratio = 1.10, 95% confidence interval = 1.06-1.13), which is intronic toPNKDandTMBIM1 Intriguingly this susceptibility SNP is in strong LD (r2= 0.90,D'= 0.96) with the previously discovered GWAS SNP rs2382817 for inflammatory bowel disease (IBD). Following on from this observation we examined for pleiotropy, or shared genetic susceptibility, between CRC and the 200 established IBD risk loci, identifying an additional 11 significant associations (FDR < 0.05). Our findings provide further insight into the biological basis of inherited genetic susceptibility to CRC, and identify risk factors that may influence the development of both CRC and IBD.
Original languageEnglish
Pages (from-to)2349-2359
JournalHuman Molecular Genetics
Issue number11
Early online date22 Mar 2016
Publication statusPublished - Jun 2016

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