Portal de Periódicos da CAPES

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

2017; Nature Portfolio; Volume: 49; Issue: 7 Linguagem: Inglês

10.1038/ng.3892

1546-1718

James 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 M. Dunning, Karen A. Pooley, David C. Qian, Xuemei Ji, Geoffrey Liu, Maria Timofeeva, Stig E. Bojesen, Xifeng Wu, Loı̈c Le Marchand, Demetrius Albanes, Heike Bickeböller, Melinda C. Aldrich, William S. Bush, Adonina Tardón, 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 Cecilia Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha B. Leighl, Jakob Sidenius Johansen, Anders Mellemgaard, Walid Saliba, Christopher A. Haiman, Lynne R. Wilkens, Ana Fernández‐Somoano, Guillermo Fernández‐Tardón, Erik H.F.M. van der Heijden, Jin Hee Kim, Juncheng Dai, Zhibin Hu, Michael 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 J. 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 Holcátová, Vladimí­r Janout, Milica Kontić, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz Orłowski, Ghislaine Scélo, Beata Świątkowska, Давид Заридзе, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J. Duell, Lesley M. Butler, Woon‐Puay Koh, Yu‐Tang Gao, Richard S. Houlston, Esther M. John, 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, Þórunn Rafnar, Thorgeir E. Thorgeirsson, Gunnar W. Reginsson, Kári Stéfansson, Dana B. Hancock, Laura J. Bierut, Margaret R. Spitz, Nathan Gaddis, Sharon M. Lutz, Fangyi Gu, Eric O. Johnson, Ahsan Kamal, Claudio W. Pikielny, Dakai Zhu, Sara Lindströem, Xia Jiang, Rachel F. Tyndale, Georgia Chenevix‐Trench, Jonathan Beesley, Yohan Bossé, Stephen J. Chanock, Paul Brennan, Maria Teresa Landi, Christopher I. Amos,

Genetic Associations and Epidemiology

Christopher Amos and colleagues perform genome-wide association analysis for lung cancer using cohorts genotyped on the OncoArray and combing these with existing data. They identify 18 loci, 10 of which are new, finding heterogeneity across the different lung cancer subtypes, and explore candidate genes through eQTL analysis in lung tissue. 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.