Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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

Orlando, Giulia, Law, Philip J., Palin, Kimmo, Tuupanen, Sari, Gylfe, Alexandra, Hänninen, Ulrika A., Cajuso, Tatiana, Tanskanen, Tomas, Kondelin, Johanna, Kaasinen, Eevi, Sarin, Antti-Pekka, Kaprio, Jaakko, Eriksson, Johan G., Rissanen, Harri, Knekt, Paul, Pukkala, Eero, Jousilahti, Pekka, Salomaa, Veikko, Ripatti, Samuli, Palotie, Aarno, Järvinen, Heikki, Renkonen-Sinisalo, Laura, Lepistö, Anna, Böhm, Jan, Mecklin, Jukka-Pekka, Al-Tassan, Nada A., Palles, Claire, Martin, Lynn, Barclay, Ella, Tenesa, Albert, Farrington, Susan, Timofeeva, Maria N., Meyer, Brian F., Wakil, Salma M., Campbell, Harry, Smith, Christopher G., Idziaszczyk, Shelley, Maughan, Timothy Stanley, Kaplan, Richard, Kerr, Rachel, Kerr, David, Buchanan, Daniel D., Ko Win, Aung, Hopper, John, Jenkins, Mark, Lindor, Noralane M., Newcomb, Polly A., Gallinger, Steve, Conti, David, Schumacher, Fred, Casey, Graham, Taipale, Jussi, Cheadle, Jeremy Peter, Dunlop, Malcolm G., Tomlinson, Ian P., Aaltonen, Lauri A. and Houlston, Richard S. 2016. Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease. Human Molecular Genetics 25 (11) , pp. 2349-2359. 10.1093/hmg/ddw087

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (557kB) | Preview

Abstract

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 to PNKD (paroxysmal non-kinesigenic dyskinesia) and TMBIM1 (transmembrane BAX inhibitor motif containing 1). Intriguingly this susceptibility single-nucleotide polymorphism (SNP) is in strong linkage disequilibrium (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 (false discovery rate [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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: colorectal cancer , inflammatory bowel disease , genetic predisposition to disease , single nucleotide polymorphism , genome-wide association study
Publisher: Oxford University Press
ISSN: 0964-6906
Date of First Compliant Deposit: 17 October 2016
Date of Acceptance: 14 March 2016
Last Modified: 04 Jun 2017 09:27
URI: http://orca-mwe.cf.ac.uk/id/eprint/95357

Citation Data

Cited 19 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics