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

• Published in: Human molecular genetics 2012-11, Vol.21 (22), p.4980-4995
• Main Authors: Timofeeva, Maria N, Hung, Rayjean J, Rafnar, Thorunn, Christiani, David C, Field, John K, Bickeböller, Heike, Risch, Angela, McKay, James D, Wang, Yufei, Dai, Juncheng, Gaborieau, Valerie, McLaughlin, John, Brenner, Darren, Narod, Steven A, Caporaso, Neil E, Albanes, Demetrius, Thun, Michael, Eisen, Timothy, Wichmann, H-Erich, Rosenberger, Albert, Han, Younghun, Chen, Wei, Zhu, Dakai, Spitz, Margaret, Wu, Xifeng, Pande, Mala, Zhao, Yang, 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, Lathrop, Mark, Benhamou, Simone, Vooder, Tõnu, Välk, Kristjan, Nelis, Mari, Metspalu, Andres, Raji, Olaide, Chen, Ying, Gosney, John, Liloglou, Triantafillos, Muley, Thomas, Dienemann, Hendrik, Thorleifsson, Gudmar, Shen, Hongbing, Stefansson, Kari, Brennan, Paul, Amos, Christopher I, Houlston, Richard, Landi, Maria Teresa
• Format: Article
• Language: English
• Subjects: Asian Continental Ancestry Group - genetics; Association Studies; Basale medisinske, odontologiske og veterinærmedisinske fag: 710; Basic medical, dental and veterinary science disciplines: 710; Case-Control Studies; European Continental Ancestry Group - genetics; Genetic Variation; Genome-Wide Association Study; Humans; Lung Neoplasms - epidemiology; Lung Neoplasms - genetics; Medical disciplines: 700; Medical genetics: 714; Medisinsk genetikk: 714; Medisinske Fag: 700; Polymorphism, Single Nucleotide; Risk; VDP
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/dds334

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.