Table 1.

Susceptibility loci for lung cancer identified by GWAS in European ancestry populations

ReferenceStudyaSample size (cases/controls)Disease/traitPlatform (# SNPs)Region (size)GeneKey SNPs
Hung et al. (14)IARC1,926/2,522Lung cancerIllumina HumanHap300 (310,023)15q25 (182 kb)CHRNA5rs1051730
Toronto330/453CHRNA3rs8034191
EPIC781/1,578CHRNB4rs16969968 (D398N)
CARET764/1,515IREB2
Liverpool403/814PSMA4
HUNT/Tromsø235/392HYKK (AGPHD1)
Thorgeirsson et al. (15)Icelandic smokers10,995Smoking quantityIllumina HumanHap300 (306,207)15q24CHRNA5rs1051730
Icelandic smokers2,950Nicotine dependenceCHRNA3
Iceland/Spain/The Netherlands1,024/32,244Lung cancerCHRNB4
Amos et al. (16)Texas1,154/1,137Non-small cell lung cancerIllumina HumanHap300 (315,450)15q25.1 (88 kb)CHRNA5rs1051730
Texas replication711/632CHRNA3rs8034191
UK2,013/3,062PSMA4rs931794
HYKK
Liu et al. (17)GELCC194/219Familial lung cancerAffymetrix 500K (399,377) or 6.0 (722,376)15q24-25.1 (160 kb)CHRNA5rs8034191
CHRNA3rs1051730
CHRNB4rs16969968 (D398N)
IREB2rs578776
PSMA4
HYKK
McKay et al. (19)Central Europe/Toronto/HUNT2-Tromso/CARET2,971/3,746Lung cancerIllumina HumanHap300 (315,194)15q25.1rs1051730
EPIC/Szczecin/CARET2/Liverpool2,899/5,5735p15.33TERTrs402710
CLPTM1Lrs2736100
Wang et al. (18)British cohort1,952/1,438Lung cancerIllumina HumanHap550 (511,919)15q25.1BAG6rs8042374
IARC1,989/2,6256p21.33 (627 kb)MSH5rs3117582
Texas1,154/1,1375p15.33 (60 kb)CLPTM1Lrs3131379
UK replication2,448/2,983rs401681
Broderick et al. (20)GELCAPS phase 11,952/1,438Lung cancerIllumina HumanHap550 (511,919)15q25.1 (248 kb)CHRNA3rs12914385
GELCAPS phase 22,465/3,005rs938682
rs8042374
rs8034191
Meta-analysis (GELCAPS, IARC, Texas)7,560/8,2055p15.33 (60 kb)CLPTM1Lrs4975616
TERT
6p21.33BAG6rs3117582
TNXBrs1150752
Landi et al. (21)NCI (EAGLE, ATBC, PLCO, CPS-II)5,739/5,848Lung cancerIllumina (515,922)15q25CHRNA3rs12914385
AdenocarcinomaCHRNA5rs1051730
Squamous cellHYKKrs8034191
Meta-analysis (UK, Central Europe, Texas, DeCODE Genetics, HGF Germany, CARET, HUNT2/Tromso, Canada, France, Estonia)13,300/19,666Small cell5p15TERTrs2736100
CLPTM1Lrs4635969
rs31489
6p21BAG6rs3117582
APOM
Timofeeva et al. (22)TRICLb14,900/29,485Lung cancerIllumina HumanHap300 (318,094) + HumanHap550 or 610Quad (217,914)15q25CHRNA5rs1051730
Han Chinese2,338/3,077CHRNA3rs8034191
CHRNB4rs6495309
HYKKrs680244
rs6495306
rs951266
5p15.33TERTrs2736100
CLPTM1Lrs401681
rs2853677
rs465498
6p21-22BAG6rs3117582
MSH5rs2523546
rs2523571
Squamous cell carcinoma12p13.33RAD52rs10849605
rs3748522
9p21.3CDKN2Ars1333040
CDKN2Brs1537372
ANRIL (CDKN2B-AS1)
2q32.1NUP35rs11683501
Wang et al. (23)MDACC ICR NCI IARC11,348/15,861Lung cancer Adenocarcinoma Squamous cell carcinomaIllumina 317, 317+240S, 370Duo, 550, 610 or 1M13q13.1BRCA2rs11571833 (K3326X)
EPIC10,246/3,8295FRYrs56084662
ICR
IARC
Toronto
22q12.1CHEK2rs17879961 (I157T)
3q28TP63rs13314271
rs4488809
McKay, Hung et al. (25)OncoArrayc29,863/55,586Lung cancerOncoarray (10,439,017)1p31.1FUBP1rs71658797
6q27RNASET2rs6920364
8p21.1EPHX2 CHRNA2rs11780471
13q13.1BRCA2rs11571833
15q21.1SEMA6Drs66759488
15q25.1CHRNA5rs55781567
19q13.2CYP2A6rs56113850
11,245/54,619Adenocarcinoma3q28TP63rs13080835
5p15.33TERTrs7705526
8p12NRG1rs4236709
9p21.3MTAP CDKN2Ars885518
10q24.3OBFC1rs11591710
11q23.3MPZL3 AMICA1rs1056562
15q21.1SECISBP2Lrs77468143
20q13.33RTEL1rs41309931
7,704/54,763Squamous cell carcinoma6p21.33MHCrs116822326
12p13.33RAD52rs7953330
22q12.1CHEK2rs17879961
Never smokers
Li et al. (34)Mayo377/377Lung cancer in never smokersIllumina HumanHap370 and HumanHap610 (331,918)13q31.3GPC5rs2352028
MDACC328/407rs2352029
Harvard92/161
UCLA91/439
Pathway-based GWAS
Shi et al. (40)NCI5,355/4,344Lung cancer Squamous cell carcinoma Adenocarcinoma, small cellIllumina (19,082) (pathway-based analysis)12p13.33RAD52rs6489769
UK1592/2,699
Texas306/1,137
UK21,038/933
Spitz et al. (41)Texas451/508NSCLC in never smokersIllumina (11,737) (pathway-based analysis)12q13ACVR1Brs12809597
Mayo303/311NR4A1rs2701129
rs1882119
Wang et al. (42)ICR12,160/16,838Lung cancerIllumina (826 functional SNPs) (pathway-based analysis)6p21.33MSH5rs3115672
MDACCGTF2H4rs114596632
IARC
NCI
Toronto
HGF Germany
5q14.2XRCC4rs1056503
rs2035990
Variant prioritization approaches
Li et al. (44)Texas1,154/1,137Lung cancer + intermediate phenotype (cigarettes per day)Illumina HumanHap30015q24-25.1HYKKrs12914385
CHRNA3
CHRNA5
CHRNB4
19q13TGFB1rs1800469
B9D2rs1982072
rs2241714
3p26rs1444056
rs1403124
Poirier et al. (45)Toronto331/499Lung cancer + family historyIllumina HumanHap300, 55010q23.33FFAR4rs12415204
IARC1,964/2,610
MDACC1,154/1,137
HMGU504/484
NCI5,699/5,815
MSH-PMH1,073/939
MEC215/225
Harvard523/497
4p15.2KCNIP4rs1158970
Brenner et al. (46)TRICLb5,061 (SQ)/6,756 (AD)/2,216 (SCLC)/33,456Squamous cell carcinomaIllumina HumanHap300, 550, 6104p15.2KCNIP4rs6448050
ILCCO625 (SQ)/1,417 (AD)/369 (SCLC)/2,966rs9799795
Adenocarcinoma18q12.1GAREMrs11662168
rs3786309
Cross-cancer loci
Hung et al. (55)GAME-ON/GECCO64,591/74,467Cross-cancerIllumina, Affymetrix (12,370) (pathway-based analysis)12q24SH2B3rs3184504 (W262R)
5p15TERTrs2736100
Fehringer et al. (56)GAME-ON/GECCO61,851/61,820Cross-cancerIllumina, Affymetrix (9,916,564)1q22MUC1rs1057941
Europeans55,789/330,490ADAM15rs4072037
Others18,152/21,410THBS3
9p21.3CDKN2B-AS1rs62560775
13q13.1BRCA2rs11571833
  • Abbreviations: ATBC, Alpha-Tocopherol, Beta-Carotene Cancer Prevention study; CARET, Beta-Carotene and Retinol Efficacy Trial; CPS-II, Cancer Prevention Study II Nutrition Cohort; EAGLE, Environment and Genetics in Lung Cancer Etiology; EPIC, European Prospective Investigation in Cancer and Nutrition; GAME-ON, The Genetic Associations and Mechanisms in Oncology; GECCO, The Genetic and Epidemiology of Colorectal Cancer Consortium; GELCAPS, Genetic Lung Cancer Predisposition Study; GELCC, Genetic Epidemiology of Lung Cancer Consortium; HGF Germany, Helmholtz-Gemeinschaft Deutscher Forschungszentren Lung Cancer GWAS; HMGU, Germany Study; HUNT, Health Study of North-Trondelag; IARC, International Agency for Research on Cancer; ICR, Institute of Cancer Research; ILCCO, International Lung Cancer Consortium; MDACC, M.D. Anderson Cancer Center; MEC, Multi-Ethnic Cohort; MSH-PMH, Mount Sinai Hospital and Princess Margaret Hospital in Toronto; NCI, National Cancer Institute; PLCO, Prostate, Lung, Colon, Ovary Screening Trial; TRICL, Transdisciplinary Research In Cancer of the Lung; UCLA, University of California in Los Angeles.

  • aItalic text indicates replication cohorts.

  • bTRICL includes the following cohorts: MDACC, Liverpool, ICR, Toronto, IARC (Central Europe, CARET, Estonia, France, HUNT2/Tromso), DeCODE Genetics, HGF Germany, Harvard, NCI (EAGLE, ATBC, PLCO, CPS-II).

  • cOncoArray includes the following cohorts: CARET, PLCO, MEC, NELCS (New England Lung Cancer Study), Harvard, MDACC, Tampa (Tampa Lung Cancer Study), BioVU (Vanderbilt 2), LCRI-DOD, TLC (Total Lung Cancer: Molecular Epidemiology of Lung Cancer Survival), Canada (Canadian Screening Study), MSH-PMH, CAPUA (Cancer de Pulmon en Asturias), ATBC, NSHDC (Northern Sweden Health and Disease Cohort), MDCS (The Malmö Diet and Cancer Study), EPIC, Liverpool, Norway (Norway Lung Cancer Study), EAGLE, Nijmegen (The Nijmegen Lung Cancer Study), NICCC-LCA (Clalit National Israeli Cancer Control Center Lung Cancer Study), L2 (The IARC L2 Study), Copenhagen (Copenhagen Lung Cancer Study), Germany, ReSoLuCENT.