Association analyses identify 31 new risk loci for colorectal cancer susceptibility

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent r...

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Detalhes bibliográficos
Autores: Law, P. J., Timofeeva, M., Fernández Rozadilla, Ceres, Broderick, P., Studd, J., Fernandez-Tajes, J., Farrington, S., Svinti, V., Palles, C., Orlando, G., Sud, A., Holroyd, A., Penegar, S., Theodoratou, E., Vaughan-Shaw, P., Campbell, H., Zgaga, L., Hayward, C., Campbell, A., Harris, S., Deary, I. J., Starr, J., Gatcombe, L., Pinna, M., Briggs, S., Martin, L., Jaeger, E., Sharma-Oates, A., East, J., Leedham, S., Arnold, R., Johnstone, E., Wang, H., Kerr, D., Kerr, R., Maughan, T., Kaplan, R., Al-Tassan, N., Palin, K., Hänninen, U. A., Cajuso, T., Tanskanen, T., Kondelin, J., Kaasinen, E., Sarin, A. P., Eriksson, J. G., Rissanen, H., Knekt, P., Pukkala, E., Jousilahti, P., Salomaa, V., Ripatti, S., Palotie, A., Renkonen-Sinisalo, L., Lepistö, A., Böhm, J., Mecklin, J. P., Buchanan, D. D., Win, A. K., Hopper, J., Jenkins, M. E., Lindor, N. M., Newcomb, P. A., Gallinger, S., Duggan, D., Casey, G., Hoffmann, P., Nöthen, M. M., Jöckel, K. H., Easton, D. F., Pharoah, P. D. P., Peto, J., Canzian, F., Swerdlow, A., Eeles, R. A., Kote-Jarai, Z., Muir, K., Pashayan, N., Henderson, B. E., Haiman, C. A., Schumacher, F. R., Al Olama, A. A., Benlloch, S., Berndt, S. I., Conti, D. V., Wiklund, F., Chanock, S., Gapstur, S., Stevens, V. L., Tangen, C. M., Batra, J., Clements, J., Gronberg, H., Schleutker, J., Albanes, D., Wolk, A., West, C., Mucci, L., Cancel-Tassin, G., Koutros, S., Sorensen, K. D., Grindedal, E. M., Neal, D. E., Hamdy, F. C., Donovan, J. L., Travis, R. C., Hamilton, R. J., Ingles, S. A., Rosenstein, B. S., Lu, Y. J., Giles, G. G., Kibel, A. S., Vega Gliemmo, Ana, Kogevinas, M., Penney, K. L., Park, J. Y., Stanford, J. L., Cybulski, C., Nordestgaard, B. G., Maier, C., Kim, J., John, E. M., Teixeira, M. R., Neuhausen, S. L., De Ruyck, K., Razack, A., Newcomb, L. F., Gamulin, M., Kaneva, R., Usmani, N., Claessens, F., Townsend, P. A., Gago-Dominguez, M., Roobol, M. J., Menegaux, F., Khaw, K. T., Cannon-Albright, L., Pandha, H., Thibodeau, S. N., Harkin, A., Allan, K., McQueen, J., Paul, J., Iveson, T., Saunders, M., Butterbach, K., Chang-Claude, J., Hoffmeister, M., Brenner, H., Kirac, I., Matošević, P., Hofer, P., Brezina, S., Gsur, A., Cheadle, J. P., Aaltonen, L. A., Tomlinson, I., Houlston, R. S., Dunlop, M. G.
Formato: artículo
Fecha de publicación:2019
País:España
Recursos:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/15791
Acesso em linha:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517433/pdf/41467_2019_Article_9775.pdf
https://www.ncbi.nlm.nih.gov/pubmed/31089142
http://hdl.handle.net/20.500.11940/15791
Access Level:acceso abierto
Palavra-chave:Risk Factors
European Continental Ancestry Group
Genetic Loci
Middle Aged
Inheritance Patterns
Humans
Genome-Wide Association Study
Case-Control Studies
Genetic Predisposition to Disease
Colorectal Neoplasms
Asian Continental Ancestry Group
grupo de ascendencia continental europea
estudios de casos y controles
gupo de ascendencia continental asiática
factores de riesgo
mediana edad
patrones de herencia
humanos
estudio de asociación genómica completa
sitios genéticos
predisposición genética a la enfermedad
neoplasias colorrectales
FPGMX
IDIS
Descrição
Resumo:Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.

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