Novel Common Genetic Susceptibility Loci for Colorectal Cancer

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...

Descripción completa

Detalles Bibliográficos
Autores: 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 C., 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.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/171985
Acceso en línea:https://hdl.handle.net/2445/171985
Access Level:acceso abierto
Palabra clave:Càncer colorectal
Genètica
Colorectal cancer
Genetics
Descripción
Sumario: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

Similares en LA Referencia