Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/171985
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.
Pharoah, Paul D.
Liu, Yun-Ru
Manion, Frank J.
Aragaki, Aaron K.
Wolk, Alicja
Shibata, David
Krogh, Vittorio
Kooperberg, Charles
Riggs, Bridget M.
Schoen, Robert E.
English, Dallas
Zubair, Niha
Gonzalez Villalpando, Clicerio
Huang, Shu-Chen
Wu, Anna H.
Brenner, Hermann
Iwasaki, Motoki
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.
Virtamo, Jarmo
Gala, Manish
Idos, Gregory E.
Cotterchio, Michelle
Hayes, Richard B.
Lin, Yi
Lu, Yingchang
Stern, Mariana C.
Loupakis, Fotios
Laurie, Cecelia A.
Figueiredo, Jane C.
McDonnell, Kevin J.
Gruber, Stephen B.
Schafmayer, Clemens
Bien, Stephanie A.
Albanes, Demetrius
Gallinger, Steven J.
Berndt, Sonja I.
Lenz, Heinz-Josef
Siegel, Erin M.
Thomas, Duncan C.
Tsugane, Shoichiro
Arndt, Volker
Hopper, John L.
Hampe, Jochen
Zanke, Brent W.
Levine, David
Carlson, Christopher S.
Lejbkowicz, Flavio
Seminara, Daniela
Woods, Michael
Marchand, Loïc Le
Hunter, David J.
Li, Li
Anton, Kristen
Matsuo, Keitaro
Duggan, David
Stintzing, Sebastian
Church, Timothy R.
Shu, Xiao-Ou
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.
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.
Giles, Graham G.
Kolonel, Laurence N.
Chin, Lee Soo
Fuchs, Charles S.
Chanock, Stephen J.
Jackson, Rebecca D.
Li, Christopher I.
Coetzee, Gerhard A.
Curtis, Keith R.
Barry, Elizabeth L.
Alonso Aguado, Maria Henar
Jiao, Shuo
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
Xiang, Yong-Bing
Hudson, Thomas J.
Haiman, Christopher A.
Ulrich, Cornelia M.
Offit, Kenneth
Luh, Frank
Boehm, Juergen
Mukherjee, Bhramar
Trichopoulou, Antonia
Qu, Conghui
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
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.
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.
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.
Severi, Gianluca
Yen, Yun
Vijai, Joseph
Peters, Ulrike
Kuehn, Tilman
Küry, Sébastien
Cheng, Ya-Wen
Southey, Melissa
Hsu, Li
Giovannucci, Edward L.
Hofer, Philipp
Melas, Marilena
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))

Files in This Item:
File Description SizeFormat 
685303.pdf350.79 kBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.