Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer

We conducted imputation to the 1000 Genomes Project of four genome-wide association studies of lung cancer in populations of European ancestry (11,348 cases and 15,861 controls) and genotyped an additional 10,246 cases and 38,295 controls for follow-up. We identified large-effect genome-wide associa...

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Detalles Bibliográficos
Autores principales: Wang, Yufei, McKay, James D., Rafnar, Thorunn, Wang, Zhaoming, Timofeeva, Maria, Broderick, Peter, Zong, Xuchen, Laplana, Marina, Wei, Yongyue, Han, Younghun, Lloyd, Amy, Delahaye-Sourdeix, Manon, Chubb, Daniel, Gaborieau, Valerie, Wheeler, William, Chatterjee, Nilanjan, Thorleifsson, Gudmar, Sulem, Patrick, Liu, Geoffrey, Kaaks, Rudolf, Henrion, Marc, Kinnersley, Ben, Vallée, Maxime, LeCalvez-Kelm, Florence, Stevens, Victoria L., Gapstur, Susan M., Chen, Wei V., Zaridze, David, Szeszenia-Dabrowska, Neonilia, Lissowska, Jolanta, Rudnai, Peter, Fabianova, Eleonora, Mates, Dana, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Krokan, Hans E., Gabrielsen, Maiken Elvestad, Skorpen, Frank, Vatten, Lars, Njølstad, Inger, Chen, Chu, Goodman, Gary, Benhamou, Simone, Vooder, Tonu, Valk, Kristjan, Nelis, Mari, Metspalu, Andres, Lener, Marcin, Lubiński, Jan, Johansson, Mattias, Vineis, Paolo, Agudo, Antonio, Clavel-Chapelon, Francoise, Bueno-de-Mesquita, H.Bas, Trichopoulos, Dimitrios, Khaw, Kay-Tee, Johansson, Mikael, Weiderpass, Elisabete, Tjønneland, Anne, Riboli, Elio, Lathrop, Mark, Scelo, Ghislaine, Albanes, Demetrius, Caporaso, Neil E., Ye, Yuanqing, Gu, Jian, Wu, Xifeng, Spitz, Margaret R., Dienemann, Hendrik, Rosenberger, Albert, Su, Li, Matakidou, Athena, Eisen, Timothy, Stefansson, Kari, Risch, Angela, Chanock, Stephen J., Christiani, David C., Hung, Rayjean J., Brennan, Paul, Landi, Maria Teresa, Houlston, Richard S., Amos, Christopher I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074058/
https://www.ncbi.nlm.nih.gov/pubmed/24880342
http://dx.doi.org/10.1038/ng.3002
Descripción
Sumario:We conducted imputation to the 1000 Genomes Project of four genome-wide association studies of lung cancer in populations of European ancestry (11,348 cases and 15,861 controls) and genotyped an additional 10,246 cases and 38,295 controls for follow-up. We identified large-effect genome-wide associations for squamous lung cancer with the rare variants of BRCA2-K3326X (rs11571833; odds ratio [OR]=2.47, P=4.74×10(−20)) and of CHEK2-I157T (rs17879961; OR=0.38 P=1.27×10(−13)). We also showed an association between common variation at 3q28 (TP63; rs13314271; OR=1.13, P=7.22×10(−10)) and lung adenocarcinoma previously only reported in Asians. These findings provide further evidence for inherited genetic susceptibility to lung cancer and its biological basis. Additionally, our analysis demonstrates that imputation can identify rare disease-causing variants having substantive effects on cancer risk from pre-existing GWAS data.

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