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Novel Common Genetic Susceptibility Loci for Colorectal Cancer. 2019
Stephanie L Schmit, and
Christopher K Edlund, and
Fredrick R Schumacher, and
Jian Gong, and
Tabitha A Harrison, and
Jeroen R Huyghe, and
Chenxu Qu, and
Marilena Melas, and
David J Van Den Berg, and
Hansong Wang, and
Stephanie Tring, and
Sarah J Plummer, and
Demetrius Albanes, and
M Henar Alonso, and
Christopher I Amos, and
Kristen Anton, and
Aaron K Aragaki, and
Volker Arndt, and
Elizabeth L Barry, and
Sonja I Berndt, and
Stéphane Bezieau, and
Stephanie Bien, and
Amanda Bloomer, and
Juergen Boehm, and
Marie-Christine Boutron-Ruault, and
Hermann Brenner, and
Stefanie Brezina, and
Daniel D Buchanan, and
Katja Butterbach, and
Bette J Caan, and
Peter T Campbell, and
Christopher S Carlson, and
Jose E Castelao, and
Andrew T Chan, and
Jenny Chang-Claude, and
Stephen J Chanock, and
Iona Cheng, and
Ya-Wen Cheng, and
Lee Soo Chin, and
James M Church, and
Timothy Church, and
Gerhard A Coetzee, and
Michelle Cotterchio, and
Marcia Cruz Correa, and
Keith R Curtis, and
David Duggan, and
Douglas F Easton, and
Dallas English, and
Edith J M Feskens, and
Rocky Fischer, and
Liesel M FitzGerald, and
Barbara K Fortini, and
Lars G Fritsche, and
Charles S Fuchs, and
Manuela Gago-Dominguez, and
Manish Gala, and
Steven J Gallinger, and
W James Gauderman, and
Graham G Giles, and
Edward L Giovannucci, and
Stephanie M Gogarten, and
Clicerio Gonzalez-Villalpando, and
Elena M Gonzalez-Villalpando, and
William M Grady, and
Joel K Greenson, and
Andrea Gsur, and
Marc Gunter, and
Christopher A Haiman, and
Jochen Hampe, and
Sophia Harlid, and
John F Harju, and
Richard B Hayes, and
Philipp Hofer, and
Michael Hoffmeister, and
John L Hopper, and
Shu-Chen Huang, and
Jose Maria Huerta, and
Thomas J Hudson, and
David J Hunter, and
Gregory E Idos, and
Motoki Iwasaki, and
Rebecca D Jackson, and
Eric J Jacobs, and
Sun Ha Jee, and
Mark A Jenkins, and
Wei-Hua Jia, and
Shuo Jiao, and
Amit D Joshi, and
Laurence N Kolonel, and
Suminori Kono, and
Charles Kooperberg, and
Vittorio Krogh, and
Tilman Kuehn, and
Sébastien Küry, and
Andrea LaCroix, and
Cecelia A Laurie, and
Flavio Lejbkowicz, and
Mathieu Lemire, and
Heinz-Josef Lenz, and
David Levine, and
Christopher I Li, and
Li Li, and
Wolfgang Lieb, and
Yi Lin, and
Noralane M Lindor, and
Yun-Ru Liu, and
Fotios Loupakis, and
Yingchang Lu, and
Frank Luh, and
Jing Ma, and
Christoph Mancao, and
Frank J Manion, and
Sanford D Markowitz, and
Vicente Martin, and
Koichi Matsuda, and
Keitaro Matsuo, and
Kevin J McDonnell, and
Caroline E McNeil, and
Roger Milne, and
Antonio J Molina, and
Bhramar Mukherjee, and
Neil Murphy, and
Polly A Newcomb, and
Kenneth Offit, and
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Domenico Palli, and
Jesus P Paredes Cotoré, and
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John D Potter, and
Conghui Qu, and
Leon Raskin, and
Gad Rennert, and
Hedy S Rennert, and
Bridget M Riggs, and
Clemens Schafmayer, and
Robert E Schoen, and
Thomas A Sellers, and
Daniela Seminara, and
Gianluca Severi, and
Wei Shi, and
David Shibata, and
Xiao-Ou Shu, and
Erin M Siegel, and
Martha L Slattery, and
Melissa Southey, and
Zsofia K Stadler, and
Mariana C Stern, and
Sebastian Stintzing, and
Darin Taverna, and
Stephen N Thibodeau, and
Duncan C Thomas, and
Antonia Trichopoulou, and
Shoichiro Tsugane, and
Cornelia M Ulrich, and
Franzel J B van Duijnhoven, and
Bethany van Guelpan, and
Joseph Vijai, and
Jarmo Virtamo, and
Stephanie J Weinstein, and
Emily White, and
Aung Ko Win, and
Alicja Wolk, and
Michael Woods, and
Anna H Wu, and
Kana Wu, and
Yong-Bing Xiang, and
Yun Yen, and
Brent W Zanke, and
Yi-Xin Zeng, and
Ben Zhang, and
Niha Zubair, and
Sun-Seog Kweon, and
Jane C Figueiredo, and
Wei Zheng, and
Loic Le Marchand, and
Annika Lindblom, and
Victor Moreno, and
Ulrike Peters, and
Graham Casey, and
Li Hsu, and
David V Conti, and
Stephen B Gruber
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
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. 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. 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. This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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Domenico Palli, and
Jesus P Paredes Cotoré, and
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Marie-Christine Boutron-Ruault, and
Hermann Brenner, and
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Koichi Matsuda, and
Keitaro Matsuo, and
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Bhramar Mukherjee, and
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Kenneth Offit, and
Hanane Omichessan, and
Domenico Palli, and
Jesus P Paredes Cotoré, and
Julyann Pérez-Mayoral, and
Paul D Pharoah, and
John D Potter, and
Conghui Qu, and
Leon Raskin, and
Gad Rennert, and
Hedy S Rennert, and
Bridget M Riggs, and
Clemens Schafmayer, and
Robert E Schoen, and
Thomas A Sellers, and
Daniela Seminara, and
Gianluca Severi, and
Wei Shi, and
David Shibata, and
Xiao-Ou Shu, and
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Franzel J B van Duijnhoven, and
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Jarmo Virtamo, and
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Alicja Wolk, and
Michael Woods, and
Anna H Wu, and
Kana Wu, and
Yong-Bing Xiang, and
Yun Yen, and
Brent W Zanke, and
Yi-Xin Zeng, and
Ben Zhang, and
Niha Zubair, and
Sun-Seog Kweon, and
Jane C Figueiredo, and
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Marilena Melas, and
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Hansong Wang, and
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Demetrius Albanes, and
M Henar Alonso, and
Christopher I Amos, and
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Amanda Bloomer, and
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Hermann Brenner, and
Stefanie Brezina, and
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Manish Gala, and
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Christopher A Haiman, and
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Flavio Lejbkowicz, and
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Hanane Omichessan, and
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Conghui Qu, and
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Gad Rennert, and
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Bridget M Riggs, and
Clemens Schafmayer, and
Robert E Schoen, and
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Yong-Bing Xiang, and
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Jane C Figueiredo, and
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Chenxu Qu, and
Marilena Melas, and
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Dallas English, and
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Manish Gala, and
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W James Gauderman, and
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Sophia Harlid, and
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Shu-Chen Huang, and
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Shuo Jiao, and
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Hedy S Rennert, and
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Clemens Schafmayer, and
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Michael Woods, and
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June 2016,
Gastroenterology,
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Chenxu Qu, and
Marilena Melas, and
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Hansong Wang, and
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M Henar Alonso, and
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Aaron K Aragaki, and
Volker Arndt, and
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Stéphane Bezieau, and
Stephanie Bien, and
Amanda Bloomer, and
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Hermann Brenner, and
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Hanane Omichessan, and
Domenico Palli, and
Jesus P Paredes Cotoré, and
Julyann Pérez-Mayoral, and
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John D Potter, and
Conghui Qu, and
Leon Raskin, and
Gad Rennert, and
Hedy S Rennert, and
Bridget M Riggs, and
Clemens Schafmayer, and
Robert E Schoen, and
Thomas A Sellers, and
Daniela Seminara, and
Gianluca Severi, and
Wei Shi, and
David Shibata, and
Xiao-Ou Shu, and
Erin M Siegel, and
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Zsofia K Stadler, and
Mariana C Stern, and
Sebastian Stintzing, and
Darin Taverna, and
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Duncan C Thomas, and
Antonia Trichopoulou, and
Shoichiro Tsugane, and
Cornelia M Ulrich, and
Franzel J B van Duijnhoven, and
Bethany van Guelpan, and
Joseph Vijai, and
Jarmo Virtamo, and
Stephanie J Weinstein, and
Emily White, and
Aung Ko Win, and
Alicja Wolk, and
Michael Woods, and
Anna H Wu, and
Kana Wu, and
Yong-Bing Xiang, and
Yun Yen, and
Brent W Zanke, and
Yi-Xin Zeng, and
Ben Zhang, and
Niha Zubair, and
Sun-Seog Kweon, and
Jane C Figueiredo, and
Wei Zheng, and
Loic Le Marchand, and
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Victor Moreno, and
Ulrike Peters, and
Graham Casey, and
Li Hsu, and
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Stephen B Gruber
April 2012,
Cancer research,
Stephanie L Schmit, and
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Chenxu Qu, and
Marilena Melas, and
David J Van Den Berg, and
Hansong Wang, and
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Demetrius Albanes, and
M Henar Alonso, and
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Volker Arndt, and
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Stéphane Bezieau, and
Stephanie Bien, and
Amanda Bloomer, and
Juergen Boehm, and
Marie-Christine Boutron-Ruault, and
Hermann Brenner, and
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Dallas English, and
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Lars G Fritsche, and
Charles S Fuchs, and
Manuela Gago-Dominguez, and
Manish Gala, and
Steven J Gallinger, and
W James Gauderman, and
Graham G Giles, and
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Stephanie M Gogarten, and
Clicerio Gonzalez-Villalpando, and
Elena M Gonzalez-Villalpando, and
William M Grady, and
Joel K Greenson, and
Andrea Gsur, and
Marc Gunter, and
Christopher A Haiman, and
Jochen Hampe, and
Sophia Harlid, and
John F Harju, and
Richard B Hayes, and
Philipp Hofer, and
Michael Hoffmeister, and
John L Hopper, and
Shu-Chen Huang, and
Jose Maria Huerta, and
Thomas J Hudson, and
David J Hunter, and
Gregory E Idos, and
Motoki Iwasaki, and
Rebecca D Jackson, and
Eric J Jacobs, and
Sun Ha Jee, and
Mark A Jenkins, and
Wei-Hua Jia, and
Shuo Jiao, and
Amit D Joshi, and
Laurence N Kolonel, and
Suminori Kono, and
Charles Kooperberg, and
Vittorio Krogh, and
Tilman Kuehn, and
Sébastien Küry, and
Andrea LaCroix, and
Cecelia A Laurie, and
Flavio Lejbkowicz, and
Mathieu Lemire, and
Heinz-Josef Lenz, and
David Levine, and
Christopher I Li, and
Li Li, and
Wolfgang Lieb, and
Yi Lin, and
Noralane M Lindor, and
Yun-Ru Liu, and
Fotios Loupakis, and
Yingchang Lu, and
Frank Luh, and
Jing Ma, and
Christoph Mancao, and
Frank J Manion, and
Sanford D Markowitz, and
Vicente Martin, and
Koichi Matsuda, and
Keitaro Matsuo, and
Kevin J McDonnell, and
Caroline E McNeil, and
Roger Milne, and
Antonio J Molina, and
Bhramar Mukherjee, and
Neil Murphy, and
Polly A Newcomb, and
Kenneth Offit, and
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International journal of molecular sciences,
