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. Author manuscript; available in PMC: 2019 Apr 15.
Published in final edited form as: Cancer Epidemiol Biomarkers Prev. 2017 Jun 14;27(4):363–379. doi: 10.1158/1055-9965.EPI-16-0794

Table 1.

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

Reference  Studya Sample size (cases/controls)  Disease/trait Platform (# SNPs) Region (size) Gene Key SNPs
Hung et al. (14)  IARC
 Toronto
 EPIC
 CARET
 Liverpool
 HUNT/Tromsø 		1926/2522
330/453
781/1578
764/1515
403/814
235/392		  Lung cancer Illumina HumanHap300
(310,023)		 15q25 (182 kb) CHRNA5
CHRNA3
CHRNB4
IREB2
PSMA4
HYKK (AGPHD1)		 rs1051730
rs8034191
rs16969968 (D398N)
Thorgeirsson et al. (15)  Icelandic smokers
 Icelandic smokers
 Iceland/Spain/The Netherlands 		10995
2950
1024/32244		  Smoking quantity
 Nicotine dependence
 Lung cancer		 Illumina HumanHap300
(306,207)		 15q24 CHRNA5
CHRNA3
CHRNB4 		rs1051730
Amos et al. (16)  Texas
 Texas replication
 UK 		1154/1137
711/632
2013/3062		  Non-small cell lung cancer Illumina HumanHap300
(315,450)		 15q25.1 (88 kb) CHRNA5
CHRNA3
PSMA4
HYKK 		rs1051730
rs8034191
rs931794
Liu et al. (17)  GELCC 194/219  Familial lung cancer Affymetrix 500K (399,377) or 6.0 (722,376) 15q24–25.1 (160 kb) CHRNA5
CHRNA3
CHRNB4
IREB2
PSMA4
HYKK 		rs8034191
rs1051730
rs16969968 (D398N)
rs578776
McKay et al. (19)  Central Europe/ Toronto/ HUNT2-Tromso/ CARET
 EPIC/Szczecin/ CARET2/ Liverpool 		2971/3746
2899/5573		  Lung cancer Illumina HumanHap300
(315,194)		 15q25.1 rs1051730
5p15.33 TERT
CLPTM1L 		rs402710
rs2736100
Wang et al. (18)  British cohort
 IARC
 Texas
 UK replication 		1952/1438
1989/2625
1154/1137
2448/2983		  Lung cancer Illumina HumanHap550
(511,919)		 15q25.1 rs8042374
6p21.33 (627 kb) BAG6
MSH5 		rs3117582
rs3131379
5p15.33 (60 kb) CLPTM1L rs401681
Broderick et al. (20)  GELCAPS phase 1
 GELCAPS phase 2
 Meta-analysis (GELCAPS, IARC, Texas) 		1952/1438
2465/3005
7560/8205		  Lung cancer Illumina HumanHap550
(511,919)		 15q25.1 (248 kb) CHRNA3 rs12914385
rs938682
rs8042374
rs8034191
5p15.33
(60 kb)		 CLPTM1L
TERT 		rs4975616
6p21.33 BAG6
TNXB 		rs3117582
rs1150752
Landi et al. (21)  NCI (EAGLE, ATBC, PLCO, CPS-II)
 Meta-analysis (UK, Central Europe, Texas, DeCODE Genetics, HGF Germany, CARET, HUNT2/Tromso, Canada, France, Estonia) 		5739/5848
13,300/19,666		  Lung cancer
 Adenocarcinoma
 Squamous cell
 Small cell		 Illumina (515,922) 15q25 CHRNA3
CHRNA5
HYKK 		rs12914385
rs1051730
rs8034191
5p15 TERT
CLPTM1L 		rs2736100 rs4635969
rs31489
6p21 BAG6
APOM 		rs3117582
Timofeeva et al. (22)  TRICLb
 Han Chinese 		14900/29485
2338/3077		  Lung cancer Illumina HumanHap300
(318,094) + HumanHap550 or 610Quad (217,914)		 15q25 CHRNA5
CHRNA3
CHRNB4
HYKK 		rs1051730
rs8034191
rs6495309
rs680244
rs6495306
rs951266
5p15.33 TERT
CLPTM1L 		rs2736100
rs401681
rs2853677
rs465498
6p21–22 BAG6
MSH5 		rs3117582
rs2523546
rs2523571
 Squamous cell carcinoma 12p13.33 RAD52 rs10849605
rs3748522
9p21.3 CDKN2A
CDKN2B
ANRIL (CDKN2B-AS1)		 rs1333040
rs1537372
2q32.1 NUP35 rs11683501
Wang et al. (23)  MDACC
 ICR
 NCI
 IARC
 EPIC
 ICR
 IARC
 Toronto 		11348/15861



10246/38295 		 Lung cancer,
Adenocarcinoma,
Squamous cell carcinoma		 Illumina 317, 317+240S, 370Duo, 550, 610 or 1M 13q13.1 BRCA2
FRY 		rs11571833 (K3326X)
rs56084662
22q12.1 CHEK2 rs17879961 (I157T)
3q28 TP63 rs13314271
rs4488809
McKay, Hung et al. (25) OncoArrayc 29863/55586  Lung cancer Oncoarray (10,439,017) 1p31.1 FUBP1 rs71658797
6q27 RNASET2 rs6920364
8p21.1 EPHX2
CHRNA2 		rs11780471
13q13.1 BRCA2 rs11571833
15q21.1 SEMA6D rs66759488
15q25.1 CHRNA5 rs55781567
19q13.2 CYP2A6 rs56113850
11245/54619  Adenocarcinoma 3q28 TP63 rs13080835
5p15.33 TERT rs7705526
8p12 NRG1 rs4236709
9p21.3 MTAP
CDKN2A 		rs885518
10q24.3 OBFC1 rs11591710
11q23.3 MPZL3
AMICA1 		rs1056562
15q21.1 SECISBP2L rs77468143
20q13.33 RTEL1 rs41309931
7704/54763  Squamous cell carcinoma 6p21.33 MHC rs116822326
12p13.33 RAD52 rs7953330
22q12.1 CHEK2 rs17879961
Never smokers
Li et al. (34)  Mayo
 MDACC
 Harvard
 UCLA 		377/377
328/407
92/161
9¼39		  Lung cancer in never smokers Illumina HumanHap370 and HumanHap610 (331,918) 13q31.3 GPC5 rs2352028
rs2352029
Pathway-based GWAS
Shi et al. (40)  NCI
 UK1
 Texas
 UK2 		5,355/4,344
592/2699
306/1137
1038/933 		Lung cancer, Squamous cell carcinoma, Adenocarcinoma, small cell Illumina (19,082) (pathway-based analysis) 12p13.33 RAD52 rs6489769
Spitz et al. (41)  Texas
 Mayo 		451/508
303/311 		 NSCLC in never smokers Illumina (11,737) (pathway-based analysis) 12q13 ACVR1B
NR4A1 		rs12809597
rs2701129
rs1882119
Wang et al. (42)  ICR
 MDACC
 IARC
 NCI
 Toronto
 HGF Germany		 12160/16838  Lung cancer Illumina (826 functional SNPs) (pathway-based analysis) 6p21.33 MSH5
GTF2H4 		rs3115672
rs114596632
5q14.2 XRCC4 rs1056503
rs2035990
Variant prioritization approaches
Li et al. (44)  Texas 1154/1137  Lung cancer + intermediate phenotype (cigarettes per day) Illumina HumanHap300 15q24–25.1 HYKK CHRNA3
CHRNA5
CHRNB4 		rs12914385
19q13 TGFB1
B9D2 		rs1800469
rs1982072
rs2241714
3p26 rs1444056
rs1403124
Poirier et al. (45)  Toronto
 IARC
 MDACC
 HMGU
 NCI
 MSH-PMH
 MEC
 Harvard 		33¼99
1964/2610
1154/1137
504/484
5699/5815
1073/939
215/225
52¾97 		 Lung cancer + Family history Illumina HumanHap300, 550 10q23.33 FFAR4 rs12415204
4p15.2 KCNIP4 rs1158970
Brenner et al. (46)  TRICLb
 ILCCO		 5061 (SQ)/ 6756 (AD)/ 2216 (SCLC)/ 33456
625 (SQ)/ 1417 (AD)/ 369 (SCLC)/ 2966 		 Squamous cell carcinoma Illumina HumanHap300, 550, 610 4p15.2 KCNIP4 rs6448050
rs9799795
 Adenocarcinoma 18q12.1 GAREM rs11662168
rs3786309
Cross-cancer loci
Hung et al. (55) GAME-ON / GECCO 64591/74467  Cross-cancer Illumina, Affymetrix
(12,370) (pathway-based analysis)		 12q24 SH2B3 rs3184504 (W262R)
5p15 TERT rs2736100
Fehringer et al. (56) GAME-ON / GECCO
Europeans
Others 		61851/61820
55789/330490
18152/21410 		 Cross-cancer Illumina, Affymetrix (9,916,564) 1q22 MUC1
ADAM15
THBS3 		rs1057941
rs4072037
9p21.3 CDKN2B-AS1 rs62560775
13q13.1 BRCA2 rs11571833

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: MD Anderson Cancer Centre; 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.

a

Italic indicates replication cohorts.

b

TRICL 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).

c

OncoArray 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.