Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes

• Verfasst von: McKay, James D. [VerfasserIn]
• Verfasst von: Muley, Thomas [VerfasserIn]
• Verfasst von: Risch, Angela [VerfasserIn]
• Titel: Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes
• Verf.angabe: James D. McKay, Rayjean J. Hung, Younghun Han, Xuchen Zong, Robert Carreras-Torres, David C. Christiani, Neil E. Caporaso, Mattias Johansson, Xiangjun Xiao, Yafang Li, Jinyoung Byun, Alison Dunning, Karen A. Pooley, David C. Qian, Xuemei Ji, Geoffrey Liu, Maria N. Timofeeva, Stig E. Bojesen, Xifeng Wu, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C. Aldrich, William S. Bush, Adonina Tardon, Gad Rennert, M. Dawn Teare, John K. Field, Lambertus A. Kiemeney, Philip Lazarus, Aage Haugen, Stephen Lam, Matthew B. Schabath, Angeline S. Andrew, Hongbing Shen, Yun-Chul Hong, Jian-Min Yuan, Pier Alberto Bertazzi, Angela C. Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha Leighl, Jakob S. Johansen, Anders Mellemgaard, Walid Saliba, Christopher A. Haiman, Lynne R. Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Henricus F. M. van der Heijden, Jin Hee Kim, Juncheng Dai, Zhibin Hu, Michael P. A. Davies, Michael W. Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C. Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Jennifer A. Doherty, Matt P. Barnett, Chu Chen, Gary E. Goodman, Angela Cox, Fiona Taylor, Penella Woll, Irene Brüske, H.-Erich Wichmann, Judith Manz, Thomas R. Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances A. Shepherd, Ming-Sound Tsao, Susanne M. Arnold, Eric B. Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M. Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J. Duell, Lesley M. Butler, Woon-Puay Koh, Yu-Tang Gao, Richard S. Houlston, John McLaughlin, Victoria L. Stevens, Philippe Joubert, Maxime Lamontagne, David C. Nickle, Ma'en Obeidat, Wim Timens, Bin Zhu, Lei Song, Linda Kachuri, María Soler Artigas, Martin D. Tobin, Louise V. Wain, SpiroMeta Consortium, Thorunn Rafnar, Thorgeir E. Thorgeirsson, Gunnar W. Reginsson, Kari Stefansson, Dana B. Hancock, Laura J. Bierut, Margaret R. Spitz, Nathan C. Gaddis, Sharon M. Lutz, Fangyi Gu, Eric O. Johnson, Ahsan Kamal, Claudio Pikielny, Dakai Zhu, Sara Lindströem, Xia Jiang, Rachel F. Tyndale, Georgia Chenevix-Trench, Jonathan Beesley, Yohan Bossé, Stephen Chanock, Paul Brennan, Maria Teresa Landi, Christopher I. Amos
• E-Jahr: 2017
• Jahr: 12 June 2017
• Umfang: 7 S.
• Fussnoten: Gesehen am 14.11.2018
• Titel Quelle: Enthalten in: Nature genetics
• Ort Quelle: London : Macmillan Publishers Limited, part of Springer Nature, 1992
• Jahr Quelle: 2017
• Band/Heft Quelle: 49(2017), 7, Seite 1126-1132
• ISSN Quelle: 1546-1718
• DOI: doi:10.1038/ng.3892
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 158371894X

Abstract

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.