Table 2 |.
Key genome-wide association studies identifying LCINS risk loci, stratified by population ancestry
| Study | Study cohorts: sample size (cases/controls) | Chromosomal region | Reference SNP cluster ID (rsID) | Associated genetic loci | OR (discovery; 95% CI) |
|---|---|---|---|---|---|
| European | |||||
| Li et al. (2010)160 | Mayo Clinic: 377/377 MDACC: 328/407 Harvard University: 92/161 UCLA: 91/439 |
13q31.3 | rs2352028 | GPC5 | 1.46 (1.26–1.70; P = 5.94 × 10−6) |
| Wang et al. (2010)338,a | Candidate gene study: 259/553 | 5p15.33 | rs4975616 | CLPTM1L–TERT | 0.69 (0.55–0.85; P = 7.95 × 10−4) |
| Sptiz et al. (2011)252,a | Pathway-based (inflammatory) association study: 451/508 | 12q13.13 | rs12809597 | ACVR1B | 0.72 (0.59–0.88; P = 0.0012) |
| Hung et al. (2019)339 | ILCCO: 3,636/6,295 | 5p15.33 | rs380286; rs31490; rs4975616 | CLPTM1L–TERT | rs380286: 0.77 (0.72–0.82; P=5.31×10−16) rs31490: 0.77 (0.72–0.82; P=4.32×10−16) rs4975616: 0.78 (0.73–0.83; P=1.04×10−14) |
| East Asian | |||||
| Hsiung et al. (2010)162,b | GELAC (Han Chinese): 584/585 GELAC (replication set): 610/560 CAMSCH: 287/287 SNU: 259/293 SWHS: 209/213 WHLCS: 207/207 KNUH: 121/119 KUMC: 95/87 GEL-S: 194/546 NJLCS: 203/203 |
5p15.33 | rs2736100 | CLPTM1L–TERT | 1.54 (1.41–1.68; P=2.60×10−20); 1.62 (1.40–1.87; P=8.51×10−11) when heterozygous; 2.54 (1.95–2.83; P=3.05×10−19) when homozygous |
| Hosgood et al. (2012)340,b | GELAC, CAMSCH, SNU, KUMC, KNUH, SWHS, GEL-S, SLCS, FLCS and TLCS: 3,467 (2,557 LUAD, 309 SCC)/3,787 in total | 3q28 | rs10937405; rs4488809 | TP63 | rs10937405: 0.80 (LUAD: 0.74–0.87; P=7.1×10−8); 0.82 (SCC: 0.67–0.99; P=0.037) rs4488809: 1.16 (LUAD: 1.08–1.24; P=7.4×10−5) |
| Shiraishi et al. (2012)341 | Japanese population study: 1,722/5,846 | 6p21.3 | rs3817963 | BTNL2 | 1.18 (1.12–1.24; P=2.7×10−10) |
| 17q24.3 | rs7216064 | BPTF | 1.20 (1.13–1.26; P=7.4×10−11) | ||
| Lan et al. (2012)163,b | FLCCA: 5,510/4,544 (from 14 studies) and 1,099/2,913 (replication set) | 10q25.2 | rs7086803 | VTI1A | 1.32 (1.24–1.41; P=5.04×10−17) |
| 6q22.2 | rs9387478 | ROS1, DCBLD1 | 0.85 (0.81–0.90; P=7.79×10−8) | ||
| 6p21.32 | rs2395185/rs28366298 | HLA class II region | 1.16 (1.09–1.23; P=2.60×10−6) | ||
| Ahn et al. (2012)171 | Korean population study: 446/497 (discovery set) and 434/1,000 (replication set) | 18p11.22 | rs11080466; rs11663246 | FAM38B (PIEZO2), APCDD1, NAPG | rs11080466: 0.61 (0.44–0.77; P=2.68×10−5) rs11663246: 0.60 (0.48–0.76; P=1.74×10−5) |
| Kim et al. (2013)175,b | Korean population study: 285/1,455 (discovery set), 294/495 (replication set 1) 546/733 (replication set 2) | 2p16.3 | rs10187911 | NRXN1 | 1.47 (1.22–1.78; P<0.001) |
| Wang et al. (2016)174,b | FLCCA: 6,877/6,277 (from 4 studies) and 5,878/7,046 (replication set) | 6p21.1 | rs7741164 | FOXP4, FOXP4–AS1 | 1.18 (1.10–1.26; P=2.05×10−6) |
| 9p21.3 | rs72658409 | CDKN2B, CDKN2B–AS1 | 0.75 (0.67–0.83; P=1.37×10−7) | ||
| 12q13.13 | rs116101143 | ACVR1B | 0.88 (0.83–0.93; P=2.21×10−6) | ||
| Shi et al. (2023)159 | FLCCA: 4,438/4,544 NJLCS: 1,923/3,544 NCC: 3,291/19,910 ACC: 1,471/2,564 |
2p23.3 | rs682888 | DTNB | 0.89 (0.86–0.93; P=4.94×10−10) |
| 3q22.2 | rs137884934 | PIK3CB | 0.81 (0.74–0.89; P=6.33×10−6) | ||
| 4p13 | rs117715768 | KCTD8 | 1.24 (1.14–1.34; P=4.48×10−7) | ||
| 4q32.1 | rs1373058 | PDGFC | 1.10 (1.05–1.15; P=8.55×10−6) | ||
| 6p12.1 | rs531557 | GCLC | 0.90 (0.87–0.94; P=7.73×10−7) | ||
| 7q31.33 | rs4268071 | GPR37 | 1.39 (1.25–1.54; P=7.27×10−10) | ||
| 10q26.13 | rs10901793 | FAM53B, METTL10 | 1.10 (1.06–1.14; P=3.14×10−7) | ||
| 11q12.2 | rs174559 | FADS1 | 0.91 (0.88–0.94; P=6.10×10−7) | ||
| 15q21.2 | rs764014 | RFX7 | 0.91 (0.88–0.95; P=5.75×10−7) | ||
| 15q21.3 | rs71467682 | FGF7, SECISBP2L | 0.91 (0.87–0.95; P=2.46×10−6) | ||
| 19p13.1 | rs116863980 | PALM | 1.31 (1.16–1.47; P=7.94×10−6) | ||
| East Asian and European | |||||
| Shi et al. (2023)159 | ILCCO multi-ancestry meta-analysis (similar effect sizes observed in both groups): 11,753/30,562 (East Asian) and 11,273/55,483 (European) | 2p11.2 | rs1130866 | SFTPB | 1.08 (P=1.56×10−8)c |
| 4q32.2 | rs2320614 | NAF1 | 1.08 (P=6.51×10−9)c | ||
| 16q23.3 | rs34638657 | MPHOSPH6 | 1.09 (P=2.19×10−9)c | ||
| 18q12.1 | rs638868 | GAREM1 | 1.08 (P=3.60×10−8)c | ||
The table lists the novel risk loci identified in each study. ACC, Aichi Cancer Center (Japan); CAMSCH, Chinese Academy of Medical Sciences Cancer Hospital; FLCCA, Female Lung Consortium in Asia; FLCS, Fudan Lung Cancer Study (China); GELAC, Genetic Epidemiological Study of Lung Adenocarcinoma (Taiwan); GEL-S, Genes and Environment in Lung Cancer, Singapore study; ILCCO, International Lung Cancer Consortium; KNUH, Kyungpook National University Hospital (South Korea); KUMC, Korea University Medical Center; LCINS, lung cancer in individuals who have never smoked; LUAD, lung adenocarcinoma; MDACC, MD Anderson Cancer Center; NCC, National Cancer Center of Japan Research Institute; NJLCS, Nanjing Lung Cancer Study (China); OR, odds ratio; SCC, squamous cell carcinoma; SLCS, Shenyang Lung Cancer Study (China); SNP, single-nucleotide polymorphism; SNU, Seoul National University (South Korea); SWHS, Shanghai Women’s Health Cohort Study (China); TLCS, Tianjin Lung Cancer Study (China); WHLCS, Wuhan Lung Cancer Study (China); UCLA, University of California Los Angeles (USA).
These studies are candidate gene and pathway-based analyses, which interrogate predefined biological pathways or gene sets; these are distinct from traditional genome-wide association studies and do not require genome-wide significance; therefore, the results should be interpreted with caution.
These studies were focused specifically on women.
No confidence intervals provided in summary statistics.