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Protein-altering germline mutations implicate novel genes related to lung cancer development
Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214407/ https://www.ncbi.nlm.nih.gov/pubmed/32393777 http://dx.doi.org/10.1038/s41467-020-15905-6 |
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author | Ji, Xuemei Mukherjee, Semanti Landi, Maria Teresa Bosse, Yohan Joubert, Philippe Zhu, Dakai Gorlov, Ivan Xiao, Xiangjun Han, Younghun Gorlova, Olga Hung, Rayjean J. Brhane, Yonathan Carreras-Torres, Robert Christiani, David C. Caporaso, Neil Johansson, Mattias Liu, Geoffrey Bojesen, Stig E. Le Marchand, Loic Albanes, Demetrios Bickeböller, Heike Aldrich, Melinda C. Bush, William S. Tardon, Adonina Rennert, Gad Chen, Chu Byun, Jinyoung Dragnev, Konstantin H. Field, John K. Kiemeney, Lambertus FA. Lazarus, Philip Zienolddiny, Shan Lam, Stephen Schabath, Matthew B. Andrew, Angeline S. Bertazzi, Pier A. Pesatori, Angela C. Diao, Nancy Su, Li Song, Lei Zhang, Ruyang Leighl, Natasha Johansen, Jakob S. Mellemgaard, Anders Saliba, Walid Haiman, Christopher Wilkens, Lynne Fernandez-Somoano, Ana Fernandez-Tardon, Guillermo Heijden, Erik H. F. M. van der Kim, Jin Hee Davies, Michael P. A. Marcus, Michael W. Brunnström, Hans Manjer, Jonas Melander, Olle Muller, David C. Overvad, Kim Trichopoulou, Antonia Tumino, Rosario Goodman, Gary E. Cox, Angela Taylor, Fiona Woll, Penella Wichmann, Erich Muley, Thomas Risch, Angela Rosenberger, Albert Grankvist, Kjell Johansson, Mikael Shepherd, Frances Tsao, Ming-Sound Arnold, Susanne M. Haura, Eric B. Bolca, Ciprian Holcatova, Ivana Janout, Vladimir Kontic, Milica Lissowska, Jolanta Mukeria, Anush Ognjanovic, Simona Orlowski, Tadeusz M. Scelo, Ghislaine Swiatkowska, Beata Zaridze, David Bakke, Per Skaug, Vidar Butler, Lesley M. Offit, Kenneth Srinivasan, Preethi Bandlamudi, Chaitanya Hellmann, Matthew D. Solit, David B. Robson, Mark E. Rudin, Charles M. Stadler, Zsofia K. Taylor, Barry S. Berger, Michael F. Houlston, Richard McLaughlin, John Stevens, Victoria Nickle, David C. Obeidat, Ma’en Timens, Wim Artigas, María Soler Shete, Sanjay Brenner, Hermann Chanock, Stephen Brennan, Paul McKay, James D. Amos, Christopher I. |
author_facet | Ji, Xuemei Mukherjee, Semanti Landi, Maria Teresa Bosse, Yohan Joubert, Philippe Zhu, Dakai Gorlov, Ivan Xiao, Xiangjun Han, Younghun Gorlova, Olga Hung, Rayjean J. Brhane, Yonathan Carreras-Torres, Robert Christiani, David C. Caporaso, Neil Johansson, Mattias Liu, Geoffrey Bojesen, Stig E. Le Marchand, Loic Albanes, Demetrios Bickeböller, Heike Aldrich, Melinda C. Bush, William S. Tardon, Adonina Rennert, Gad Chen, Chu Byun, Jinyoung Dragnev, Konstantin H. Field, John K. Kiemeney, Lambertus FA. Lazarus, Philip Zienolddiny, Shan Lam, Stephen Schabath, Matthew B. Andrew, Angeline S. Bertazzi, Pier A. Pesatori, Angela C. Diao, Nancy Su, Li Song, Lei Zhang, Ruyang Leighl, Natasha Johansen, Jakob S. Mellemgaard, Anders Saliba, Walid Haiman, Christopher Wilkens, Lynne Fernandez-Somoano, Ana Fernandez-Tardon, Guillermo Heijden, Erik H. F. M. van der Kim, Jin Hee Davies, Michael P. A. Marcus, Michael W. Brunnström, Hans Manjer, Jonas Melander, Olle Muller, David C. Overvad, Kim Trichopoulou, Antonia Tumino, Rosario Goodman, Gary E. Cox, Angela Taylor, Fiona Woll, Penella Wichmann, Erich Muley, Thomas Risch, Angela Rosenberger, Albert Grankvist, Kjell Johansson, Mikael Shepherd, Frances Tsao, Ming-Sound Arnold, Susanne M. Haura, Eric B. Bolca, Ciprian Holcatova, Ivana Janout, Vladimir Kontic, Milica Lissowska, Jolanta Mukeria, Anush Ognjanovic, Simona Orlowski, Tadeusz M. Scelo, Ghislaine Swiatkowska, Beata Zaridze, David Bakke, Per Skaug, Vidar Butler, Lesley M. Offit, Kenneth Srinivasan, Preethi Bandlamudi, Chaitanya Hellmann, Matthew D. Solit, David B. Robson, Mark E. Rudin, Charles M. Stadler, Zsofia K. Taylor, Barry S. Berger, Michael F. Houlston, Richard McLaughlin, John Stevens, Victoria Nickle, David C. Obeidat, Ma’en Timens, Wim Artigas, María Soler Shete, Sanjay Brenner, Hermann Chanock, Stephen Brennan, Paul McKay, James D. Amos, Christopher I. |
author_sort | Ji, Xuemei |
collection | PubMed |
description | Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10(−15)) and replication (adjusted OR = 2.93, P = 2.22 × 10(−3)) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR = 2.61, P = 7.98 × 10(−22)) and replication datasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. |
format | Online Article Text |
id | pubmed-7214407 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72144072020-05-14 Protein-altering germline mutations implicate novel genes related to lung cancer development Ji, Xuemei Mukherjee, Semanti Landi, Maria Teresa Bosse, Yohan Joubert, Philippe Zhu, Dakai Gorlov, Ivan Xiao, Xiangjun Han, Younghun Gorlova, Olga Hung, Rayjean J. Brhane, Yonathan Carreras-Torres, Robert Christiani, David C. Caporaso, Neil Johansson, Mattias Liu, Geoffrey Bojesen, Stig E. Le Marchand, Loic Albanes, Demetrios Bickeböller, Heike Aldrich, Melinda C. Bush, William S. Tardon, Adonina Rennert, Gad Chen, Chu Byun, Jinyoung Dragnev, Konstantin H. Field, John K. Kiemeney, Lambertus FA. Lazarus, Philip Zienolddiny, Shan Lam, Stephen Schabath, Matthew B. Andrew, Angeline S. Bertazzi, Pier A. Pesatori, Angela C. Diao, Nancy Su, Li Song, Lei Zhang, Ruyang Leighl, Natasha Johansen, Jakob S. Mellemgaard, Anders Saliba, Walid Haiman, Christopher Wilkens, Lynne Fernandez-Somoano, Ana Fernandez-Tardon, Guillermo Heijden, Erik H. F. M. van der Kim, Jin Hee Davies, Michael P. A. Marcus, Michael W. Brunnström, Hans Manjer, Jonas Melander, Olle Muller, David C. Overvad, Kim Trichopoulou, Antonia Tumino, Rosario Goodman, Gary E. Cox, Angela Taylor, Fiona Woll, Penella Wichmann, Erich Muley, Thomas Risch, Angela Rosenberger, Albert Grankvist, Kjell Johansson, Mikael Shepherd, Frances Tsao, Ming-Sound Arnold, Susanne M. Haura, Eric B. Bolca, Ciprian Holcatova, Ivana Janout, Vladimir Kontic, Milica Lissowska, Jolanta Mukeria, Anush Ognjanovic, Simona Orlowski, Tadeusz M. Scelo, Ghislaine Swiatkowska, Beata Zaridze, David Bakke, Per Skaug, Vidar Butler, Lesley M. Offit, Kenneth Srinivasan, Preethi Bandlamudi, Chaitanya Hellmann, Matthew D. Solit, David B. Robson, Mark E. Rudin, Charles M. Stadler, Zsofia K. Taylor, Barry S. Berger, Michael F. Houlston, Richard McLaughlin, John Stevens, Victoria Nickle, David C. Obeidat, Ma’en Timens, Wim Artigas, María Soler Shete, Sanjay Brenner, Hermann Chanock, Stephen Brennan, Paul McKay, James D. Amos, Christopher I. Nat Commun Article Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10(−15)) and replication (adjusted OR = 2.93, P = 2.22 × 10(−3)) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR = 2.61, P = 7.98 × 10(−22)) and replication datasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. Nature Publishing Group UK 2020-05-11 /pmc/articles/PMC7214407/ /pubmed/32393777 http://dx.doi.org/10.1038/s41467-020-15905-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ji, Xuemei Mukherjee, Semanti Landi, Maria Teresa Bosse, Yohan Joubert, Philippe Zhu, Dakai Gorlov, Ivan Xiao, Xiangjun Han, Younghun Gorlova, Olga Hung, Rayjean J. Brhane, Yonathan Carreras-Torres, Robert Christiani, David C. Caporaso, Neil Johansson, Mattias Liu, Geoffrey Bojesen, Stig E. Le Marchand, Loic Albanes, Demetrios Bickeböller, Heike Aldrich, Melinda C. Bush, William S. Tardon, Adonina Rennert, Gad Chen, Chu Byun, Jinyoung Dragnev, Konstantin H. Field, John K. Kiemeney, Lambertus FA. Lazarus, Philip Zienolddiny, Shan Lam, Stephen Schabath, Matthew B. Andrew, Angeline S. Bertazzi, Pier A. Pesatori, Angela C. Diao, Nancy Su, Li Song, Lei Zhang, Ruyang Leighl, Natasha Johansen, Jakob S. Mellemgaard, Anders Saliba, Walid Haiman, Christopher Wilkens, Lynne Fernandez-Somoano, Ana Fernandez-Tardon, Guillermo Heijden, Erik H. F. M. van der Kim, Jin Hee Davies, Michael P. A. Marcus, Michael W. Brunnström, Hans Manjer, Jonas Melander, Olle Muller, David C. Overvad, Kim Trichopoulou, Antonia Tumino, Rosario Goodman, Gary E. Cox, Angela Taylor, Fiona Woll, Penella Wichmann, Erich Muley, Thomas Risch, Angela Rosenberger, Albert Grankvist, Kjell Johansson, Mikael Shepherd, Frances Tsao, Ming-Sound Arnold, Susanne M. Haura, Eric B. Bolca, Ciprian Holcatova, Ivana Janout, Vladimir Kontic, Milica Lissowska, Jolanta Mukeria, Anush Ognjanovic, Simona Orlowski, Tadeusz M. Scelo, Ghislaine Swiatkowska, Beata Zaridze, David Bakke, Per Skaug, Vidar Butler, Lesley M. Offit, Kenneth Srinivasan, Preethi Bandlamudi, Chaitanya Hellmann, Matthew D. Solit, David B. Robson, Mark E. Rudin, Charles M. Stadler, Zsofia K. Taylor, Barry S. Berger, Michael F. Houlston, Richard McLaughlin, John Stevens, Victoria Nickle, David C. Obeidat, Ma’en Timens, Wim Artigas, María Soler Shete, Sanjay Brenner, Hermann Chanock, Stephen Brennan, Paul McKay, James D. Amos, Christopher I. Protein-altering germline mutations implicate novel genes related to lung cancer development |
title | Protein-altering germline mutations implicate novel genes related to lung cancer development |
title_full | Protein-altering germline mutations implicate novel genes related to lung cancer development |
title_fullStr | Protein-altering germline mutations implicate novel genes related to lung cancer development |
title_full_unstemmed | Protein-altering germline mutations implicate novel genes related to lung cancer development |
title_short | Protein-altering germline mutations implicate novel genes related to lung cancer development |
title_sort | protein-altering germline mutations implicate novel genes related to lung cancer development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214407/ https://www.ncbi.nlm.nih.gov/pubmed/32393777 http://dx.doi.org/10.1038/s41467-020-15905-6 |
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