Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls.

Abstract

Recent genome-wide association studies (GWASs) have identified common genetic variants at 5p15.33, 6p21-6p22 and 15q25.1 associated with lung cancer risk. Several other genetic regions including variants of CHEK2 (22q12), TP53BP1 (15q15) and RAD52 (12p13) have been demonstrated to influence lung cancer risk in candidate- or pathway-based analyses. To identify novel risk variants for lung cancer, we performed a meta-analysis of 16 GWASs, totaling 14 900 cases and 29 485 controls of European descent. Our data provided increased support for previously identified risk loci at 5p15 (P = 7.2 × 10(-16)), 6p21 (P = 2.3 × 10(-14)) and 15q25 (P = 2.2 × 10(-63)). Furthermore, we demonstrated histology-specific effects for 5p15, 6p21 and 12p13 loci but not for the 15q25 region. Subgroup analysis also identified a novel disease locus for squamous cell carcinoma at 9p21 (CDKN2A/p16(INK4A)/p14(ARF)/CDKN2B/p15(INK4B)/ANRIL; rs1333040, P = 3.0 × 10(-7)) which was replicated in a series of 5415 Han Chinese (P = 0.03; combined analysis, P = 2.3 × 10(-8)). This large analysis provides additional evidence for the role of inherited genetic susceptibility to lung cancer and insight into biological differences in the development of the different histological types of lung cancer.

• Authors: Maria N Timofeeva, Rayjean J Hung, Thorunn Rafnar, David C Christiani, John K Field, Heike Bickeböller, Angela Risch, James D McKay, Yufei Wang, Juncheng Dai, Valerie Gaborieau, John McLaughlin, Darren Brenner, Steven A Narod, Neil E Caporaso, Demetrius Albanes, Michael Thun, Timothy Eisen, H-Erich Wichmann, Albert Rosenberger, Younghun Han, Wei Chen, Dakai Zhu, Margaret Spitz, Xifeng Wu, Mala Pande, Yang Zhao, David Zaridze, Neonilia Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Dana Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Hans E Krokan, Maiken Elvestad Gabrielsen, Frank Skorpen, Lars Vatten, Inger Njølstad, Chu Chen, Gary Goodman, Mark Lathrop, Simone Benhamou, Tõnu Vooder, Kristjan Välk, Mari Nelis, Andres Metspalu, Olaide Raji, Ying Chen, John Gosney, Triantafillos Liloglou, Thomas Muley, Hendrik Dienemann, Gudmar Thorleifsson, Hongbing Shen, Kari Stefansson, Paul Brennan, Christopher I Amos, Richard Houlston, Maria Teresa Landi, Transdisciplinary Research in Cancer of the Lung (TRICL) Research Team
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 21 Issue 22 Pg. 4980-95 (Nov 15 2012) ISSN: 1460-2083 [Electronic] England
• PMID: 22899653 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Topics

• Asian People (genetics)
• Case-Control Studies
• Genetic Variation
• Genome-Wide Association Study
• Humans
• Lung Neoplasms (epidemiology, genetics)
• Polymorphism, Single Nucleotide
• Risk
• White People (genetics)