期刊
JOURNAL OF THORACIC ONCOLOGY
卷 14, 期 8, 页码 1360-1369出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jtho.2019.04.008
关键词
Lung cancer; Never smokers; Genome-wide association study; Genetic susceptibility
资金
- National Institutes of Health (NIH) [CA149462, CA209414, CA092824, ES00002, U01CA209414, U19CA203654, 1K07CA172294, P50CA119997, R01CA060691, R01CA87895, P30CA22453, P30CA008748, P30CA076292, U01CA164973]
- Department of Health and Human Services [HHSN261201300011]
- James & Esther King Biomedical Research Program [09KN-15]
- Helmholtz-DAAD fellowship [A/07/97379]
- Society of Memorial Sloan Kettering Cancer Center
- Associazione Italiana per la Ricerca sul Cancro [IG2015/17564IO]
- Instituto de Salud Carlos III [PI15/01211]
- Xunta de Galicia [10CSA208057PR]
- Canadian Cancer Society Research Institute [020214]
- Alan Brown Chair Program at the Princess Margaret Hospital Foundation
- Lusi Wong Program at the Princess Margaret Hospital Foundation
- Germany National Genome Research Network (NGFN)
- DFG [BI576/2-1, BI 576/2-2, Bi 576/4-1, Bi 576/4-2, Wi 621/10-1, Wi 621/10-2]
- Helmholtzgemeinschaft (HGF)
- Federal office for Radiation Protection [BfS: STSch4454]
- Helmholtz-Zentrum Munchen (HMGU)
- Roy Castle Lung Cancer Foundation
- Sheffield Experimental Cancer Medicine Centre
- Weston Park Hospital Cancer Charity
- Canada Research Chair
- Cancer Prevention Research Institute of Texas [RR170048]
- German Federal Ministry of Education, Science, Research and Technology
- State of Bavaria
- Sheffield Hospitals Charity
- Italian Ministry of Health grant for Institutional Research 2017-2018
- NATIONAL CANCER INSTITUTE [ZIABC011555] Funding Source: NIH RePORTER
Introduction: Inherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer. Methods: We conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer. Results: We detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722-0.820; p value 5.31 x 10(-16)), rs380286 (OR: 0.770, 95% CI: 0.723-0.820; p value 4.32 x 10(-16)), and rs4975616 OR: 0.778, 95% CI: 0.730-0.829; p value 1.04 x 10(-14)). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate. Conclusions: We found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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