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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Main Authors:	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.
Format:	Online
Language:	English
Published:	2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074058/

id	pubmed-4074058
recordtype	oai_dc
spelling	pubmed-40740582015-01-01 Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer 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. Article 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. 2014-06-01 2014-07 /pmc/articles/PMC4074058/ /pubmed/24880342 http://dx.doi.org/10.1038/ng.3002 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	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.
spellingShingle	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. Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer
author_facet	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.
author_sort	Wang, Yufei
title	Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer
title_short	Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer
title_full	Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer
title_fullStr	Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer
title_full_unstemmed	Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer
title_sort	rare variants of large effect in brca2 and chek2 affect risk of lung cancer
description	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.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074058/
_version_	1612107276979535872

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

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