Title: | Novel Common Genetic Susceptibility Loci for Colorectal Cancer |
Author: | Schmit, Stephanie L. Edlund, Christopher K. Schumacher, Fredrick R. Gong, Jian Harrison, Tabitha A. Huyghe, Jeroen R. Qu, Chenxu Van Den Berg, David J. Wang, Hansong Tring, Stephanie Plummer, Sarah J. Melas, Marilena Riggs, Bridget M. Schoen, Robert E. English, Dallas R. Zubair, Niha Gonzalez Villalpando, Clicerio Huang, Shu-Chen Wu, Anna H. Brenner, Hermann Iwasaki, Motoki Chin, Lee Soo Fortini, Barbara K. Stadler, Zsofia K. Huerta Castaño, José María Ma, Jing Paredes Cotoré, Jesus P. Amos, Christopher I. Newcomb, Polly A. Cheng, Iona Sellers, Thomas A. Grady, William M. Fuchs, Charles S. Virtamo, Jarmo Gala, Manish Idos, Gregory E. Cotterchio, Michelle Hayes, Richard B. Lin, Yi Lu, Yingchang Stern, Mariana C. Loupakis, Fotios Laurie, Cecelia A. Chanock, Stephen J. Figueiredo, Jane C. McDonnell, Kevin J. Gruber, Stephen B. Schafmayer, Clemens Bien, Stephanie A. Albanes, Demetrius Gallinger, Steven Berndt, Sonja I. Lenz, Heinz-Josef Siegel, Erin M. Jackson, Rebecca D. Thomas, Duncan C. Tsugane, Shoichiro Arndt, Volker Hopper, John L. Hampe, Jochen Zanke, Brent W. Levine, David Carlson, Christopher S. Lejbkowicz, Flavio Seminara, Daniela Li, Christopher I. Woods, Michael Marchand, Loïc Le Hunter, David J. Li, Li Anton, Kristen Matsuo, Keitaro Duggan, David Stintzing, Sebastian Church, Timothy R. Shu, Xiao-Ou Coetzee, Gerhard A. Milne, Roger L. Castelao, Jose E. Lieb, Wolfgang Thibodeau, Stephen N. Jacobs, Eric J. Raskin, Leon Boutron-Ruault, Marie-Christine Zhang, Ben Caan, Bette J. Potter, John D. Curtis, Keith R. Moreno Aguado, Víctor Chan, Andrew T. LaCroix, Andrea Win, Aung Ko Gogarten, Stephanie M. Rennert, Hedy S. Casey, Graham Matsuda, Koichi Slattery, Martha L. Harju, John F. Barry, Elizabeth L. Giles, Graham G. Kolonel, Laurence N. Alonso Aguado, Maria Henar Jiao, Shuo Pharoah, Paul D. Palli, Domenico Campbell, Peter T. Markowitz, Sanford D. Mancao, Christoph Correa, Marcia Cruz Bézieau, Stéphane Feskens, Edith J. M. Gsur, Andrea Brezina, Stefanie Kweon, Sun-Seog Liu, Yun-Ru Xiang, Yong-Bing Hudson, Thomas J. Haiman, Christopher A. Ulrich, Cornelia M. Offit, Kenneth Luh, Frank Boehm, Juergen Mukherjee, Bhramar Trichopoulou, Antonia Qu, Conghui Manion, Frank J. Gauderman, W. James Chang-Claude, Jenny Shi, Wei Greenson, Joel K. Bloomer, Amanda van Duijnhoven, Franzel J. B. Conti, David V. Rennert, Gad Jenkins, Mark A. Wu, Kana Aragaki, Aaron K. Taverna, Darin Lindor, Noralane M. Harlid, Sophia Zheng, Wei Kono, Suminori Molina de la Torre, Antonio José Buchanan, Daniel D. Gunter, Marc Jia, Wei-Hua McNeil, Caroline E. Wolk, Alicja Jee, Sun Ha Weinstein, Stephanie J. Zeng, Yi-Xin White, Emily Joshi, Amit D. Butterbach, Katja Gonzalez Villalpando, Elena M. Fischer, Rocky Omichessan, Hanane Easton, Douglas F. Shibata, David Hoffmeister, Michael Lindblom, Annika Lemire, Mathieu Fritsche, Lars G. Church, James M. Martín Sánchez, Vicente van Guelpan, Bethany Pérez-Mayoral, Julyann Gago-Dominguez, Manuela FitzGerald, Liesel M. Krogh, Vittorio Severi, Gianluca Yen, Yun Vijai, Joseph Peters, Ulrike Kuehn, Tilman Küry, Sébastien Cheng, Ya-Wen Southey, Melissa Hsu, Li Giovannucci, Edward L. Kooperberg, Charles Hofer, Philipp |
Keywords: | Càncer colorectal Genètica Colorectal cancer Genetics |
Issue Date: | 16-Jun-2018 |
Publisher: | Oxford University Press |
Abstract: | BACKGROUND: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. METHODS: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. RESULTS: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. CONCLUSIONS: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening |
Note: | Versió postprint del document publicat a: https://doi.org/10.1093/jnci/djy099 |
It is part of: | JNCI: Journal of The National Cancer Institute, 2018, vol. 111, num. 2, p. 146-157 |
URI: | http://hdl.handle.net/2445/171985 |
Related resource: | https://doi.org/10.1093/jnci/djy099 |
ISSN: | 0027-8874 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.