| Title: |
Novel Common Genetic Susceptibility Loci for Colorectal Cancer |
| Authors: |
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.; Kolonel, Laurence N.; Alonso Aguado, Maria Henar; Jiao, Shuo; Pharoah, Paul D. P.; Palli, Domenico; Campbell, Peter T.; Markowitz, Sanford D.; Mancao, Christoph; Correa, Marcia Cruz; Bézieau, Stéphane; Melas, Marilena; 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; Riggs, Bridget M.; Luh, Frank; Boehm, Juergen; Mukherjee, Bhramar; Trichopoulou, Antonia; Qu, Conghui; Manion, Frank J.; Gauderman, W. James; Chang-Claude, Jenny; Shi, Wei; Greenson, Joel K.; Schoen, Robert E.; 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; English, Dallas R.; Zheng, Wei; Kono, Suminori; Molina de la Torre, Antonio José; Buchanan, Daniel D.; Gunter, Marc J.; Jia, Wei-Hua; McNeil, Caroline E.; Wolk, Alicja; Jee, Sun Ha; Weinstein, Stephanie J.; Zubair, Niha; 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; Gonzalez Villalpando, Clicerio; 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; Huang, Shu-Chen; Severi, Gianluca; Yen, Yun; Vijai, Joseph; Peters, Ulrike; Kuehn, Tilman; Küry, Sébastien; Cheng, Ya-Wen; Southey, Melissa; Hsu, Li; Giovannucci, Edward L.; Wu, Anna H.; Kooperberg, Charles; Hofer, Philipp; 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. |
| Source: |
Articles publicats en revistes (Ciències Clíniques) |
| Publisher Information: |
Oxford University Press |
| Publication Year: |
2018 |
| Collection: |
Dipòsit Digital de la Universitat de Barcelona |
| Subject Terms: |
Càncer colorectal; Genètica; Colorectal cancer; Genetics |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
12 p.; application/pdf |
| Language: |
English |
| Relation: |
Versió postprint del document publicat a: https://doi.org/10.1093/jnci/djy099; JNCI: Journal of The National Cancer Institute, 2018, vol. 111, num. 2, p. 146-157; https://doi.org/10.1093/jnci/djy099; https://hdl.handle.net/2445/171985; 685303 |
| Availability: |
https://hdl.handle.net/2445/171985 |
| Rights: |
(c) Schmit, Stephanie L. et al., 2018 ; info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.43AD2ABA |
| Database: |
BASE |