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.
Gallinger, Steven J.
Alonso Aguado, Maria Henar
Xiang, Yong-Bing
Shi, Wei
Kono, Suminori
Gonzalez Villalpando, Elena M.
Gago-Dominguez, Manuela
Melas, Marilena
Correa, Marcia Cruz
Luh, Frank
Conti, David V.
Gunter, Marc
Omichessan, Hanane
FitzGerald, Liesel M.
Hofer, Philipp
Liu, Yun-Ru
Manion, Frank J.
Wolk, Alicja
Shibata, David
Krogh, Vittorio
Kooperberg, Charles
Riggs, Bridget M.
Schoen, Robert E.
Zubair, Niha
Gonzalez Villalpando, Clicerio
Huang, Shu-Chen
Wu, Anna H.
Iwasaki, Motoki
Fortini, Barbara K.
Stadler, Zsofia K.
Huerta Castaño, José María
Ma, Jing
Amos, Christopher I.
Newcomb, Polly A.
Cheng, Iona
Sellers, Thomas A.
Grady, William M.
Gala, Manish
Idos, Gregory E.
Cotterchio, Michelle
Hayes, Richard B.
Lu, Yingchang
Stern, Mariana C.
Loupakis, Fotios
Laurie, Cecelia A.
Figueiredo, Jane C.
McDonnell, Kevin J.
Schafmayer, Clemens
Bien, Stephanie A.
Albanes, Demetrius
Berndt, Sonja I.
Lenz, Heinz-Josef
Siegel, Erin M.
Thomas, Duncan C.
Tsugane, Shoichiro
Arndt, Volker
Hopper, John L.
Zanke, Brent W.
Levine, David
Lejbkowicz, Flavio
Seminara, Daniela
Woods, Michael
Marchand, Loic Le
Hunter, David J.
Li, Li
Anton, Kristen
Matsuo, Keitaro
Stintzing, Sebastian
Shu, Xiao-Ou
Milne, Roger
Castelao, Jose E.
Lieb, Wolfgang
Thibodeau, Stephen N.
Jacobs, Eric J.
Raskin, Leon
Boutron-Ruault, Marie-Christine
Zhang, Ben
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.
Chin, Lee Soo
English, Dallas
Aragaki, Aaron K.
Brenner, Hermann
Virtamo, Jarmo
Gruber, Stephen B.
Hampe, Jochen
Duggan, David
Caan, Bette J.
Kolonel, Laurence N.
Paredes Cotoré, Jesus P.
Lin, Yi
Carlson, Christopher S.
Church, Timothy R.
Potter, John D.
Giles, Graham G.
Fuchs, Charles S.
Chanock, Stephen J.
Li, Christopher I.
Coetzee, Gerhard A.
Curtis, Keith R.
Barry, Elizabeth L.
Jiao, Shuo
Palli, Domenico
Campbell, Peter T.
Markowitz, Sanford D.
Mancao, Christoph
Bézieau, Stéphane
Feskens, Edith J. M.
Gsur, Andrea
Brezina, Stefanie
Kweon, Sun-Seog
Hudson, Thomas J.
Haiman, Christopher A.
Ulrich, Cornelia M.
Offit, Kenneth
Boehm, Juergen
Mukherjee, Bhramar
Trichopoulou, Antonia
Qu, Conghui
Gauderman, W. James
Chang-Claude, Jenny
Greenson, Joel K.
Bloomer, Amanda
van Duijnhoven, Franzel J. B.
Rennert, Gad
Jenkins, Mark A.
Wu, Kana
Taverna, Darin
Lindor, Noralane M.
Harlid, Sophia
Zheng, Wei
Molina, Antonio J.
Buchanan, Daniel D.
Jia, Wei-Hua
McNeil, Caroline E.
Jee, Sun Ha
Weinstein, Stephanie J.
Zeng, Yi-Xin
White, Emily
Joshi, Amit D.
Butterbach, Katja
Fischer, Rocky
Easton, Douglas F.
Hoffmeister, Michael
Lindblom, Annika
Lemire, Mathieu
Fritsche, Lars G.
Church, James M.
Martin, Vicente
van Guelpan, Bethany
Pérez-Mayoral, Julyann
Severi, Gianluca
Yen, Yun
Vijai, Joseph
Peters, Ulrike
Kuehn, Tilman
Küry, Sébastien
Cheng, Ya-Wen
Southey, Melissa
Hsu, Li
Giovannucci, Edward L.
Pharoah, Paul D.
Jackson, Rebecca D.
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))

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