Lung cancer overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammad Braizat, M.S. [2]
Overview
Lung cancer is a malignant epithelial tumor of the lung that is not a single disease but two biologically and therapeutically distinct entities: non–small cell lung cancer (NSCLC, ~85%) and small cell lung cancer (SCLC, ~15%).[1][2] The single most important change from legacy teaching is that lung cancer is no longer managed as one disease: histologic subtype, molecular driver status, and PD-L1 expression now dictate therapy in advanced disease, and low-dose CT (LDCT) screening plus stage-shift have begun to bend the mortality curve.[3][4]
This microchapter covers risk factors and relevant contextual data for lung cancer. Definition, classification, epidemiology, screening, diagnosis, staging, treatment, and prognosis are summarized only as needed for context and are detailed in their dedicated microchapters.
Burden and contextual data
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide — approximately 2.48 million new cases and 1.8 million deaths in 2022, with the global burden projected to rise toward 4.6 million cases and 3.5 million deaths by 2050 absent intervention.[5][6] In the US it remains the leading cause of cancer death despite falling incidence.[7] US lung cancer death rates are declining faster than incidence; the ACS reports the 2014–2020 mortality decline accelerated to approximately −5.3%/year in men and −4.3%/year in women, reflecting reduced smoking, earlier-stage diagnosis, and improved therapy.[8] Detailed demographics and secular trends belong in the Epidemiology microchapter.
Risk factors
Tobacco smoking (dominant cause)
Cigarette smoking is the single most important cause of lung cancer, accounting for roughly 80–90% of cases and an ~85% population-attributable fraction in the US, with a 10- to 30-fold (≈20-fold) relative risk versus never-smokers.[9][10][11] Risk rises with cumulative exposure in a nonlinear dose-response: mean relative risk ≈5.1 at 20 pack-years and ≈13.4 at ~51 pack-years, with diminishing marginal risk beyond ~40 pack-years.[12] Risk declines with sustained cessation.[9][12] Cigars, pipes, and bidis also cause lung cancer.[9]
Secondhand smoke
Living with a person who smokes increases non-smoker risk by ~20–30% and is responsible for an estimated ~3,500 US non-smoker lung cancer deaths annually (~2.7% of US lung cancer cases).[9][10]
Radon
Radon is the second-leading cause overall and the leading environmental cause in never-smokers (~12% of US lung cancers; up to ~21,000 deaths/year).[13][10] The EPA recommends mitigation at ≥4 pCi/L (150 Bq/m³) and consideration between 2–4 pCi/L.[10]
Occupational and environmental exposures
Established occupational carcinogens include asbestos, arsenic, chromium, nickel, beryllium, cadmium, silica dust, diesel exhaust, and ionizing radiation; several act independently of and multiplicatively with smoking.[9][11] Ambient air pollution (PM2.5; IARC group 1) and household solid-fuel/cooking-oil fumes are additional contributors, particularly in never-smoking women.[13][10]
Host and genetic factors
Family history of lung cancer in a first-degree relative confers an ~2–4× risk. COPD, pulmonary fibrosis, prior thoracic radiotherapy, East Asian female ancestry, and germline variants also increase risk.[11][13][14] Approximately 15–25% of lung cancers occur in never-smokers, a growing proportion, with higher rates of targetable EGFR and ALK alterations.[13][15][14]
Modifiable versus nonmodifiable risk
| Category | Factors | Notes |
|---|---|---|
| Modifiable | Tobacco smoking; secondhand smoke; radon; occupational carcinogens; air pollution; household solid fuels | ~73% of lung cancer cases are attributable to modifiable factors, with smoking the dominant contributor (PAF ~64%) |
| Nonmodifiable / host | Family history; COPD; pulmonary fibrosis; prior thoracic radiotherapy; East Asian female ancestry; germline variants | Family history in a first-degree relative confers ~2–4× risk |
Screening eligibility (pointer)
Annual LDCT screening is recommended for eligible high-risk adults (USPSTF Grade B: age 50–80 years, ≥20 pack-years, currently smoking or quit within 15 years). Eligibility thresholds, Lung-RADS management, and shared decision-making belong in the Screening microchapter.[4][8]
References
- ↑ Reck M, Rabe KF (2017). "Precision Diagnosis and Treatment for Advanced Non–Small-Cell Lung Cancer". N Engl J Med. 377 (9): 849–861. doi:10.1056/NEJMra1703413. PMID 28854079.
- ↑ Sasaki T, Kuno H, Hiyama T; et al. (2024). "2021 WHO Classification of Lung Cancer: Molecular Biology Research and Radiologic-Pathologic Correlation". Radiographics. 44 (3): e230136. doi:10.1148/rg.230136. PMID 38358916 Check
|pmid=value (help). - ↑ Henley SJ, Siegel DA, Firth AU; et al. (2026). "Annual Report to the Nation on the Status of Cancer, Featuring 21st Century Progress Against Lung Cancer". Cancer. 132 (19): e70577. doi:10.1002/cncr.70577.
- ↑ 4.0 4.1 US Preventive Services Task Force, Krist AH, Davidson KW; et al. (2021). "Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement". JAMA. 325 (10): 962–970. doi:10.1001/jama.2021.1117. PMID 33687470 Check
|pmid=value (help). - ↑ Zhou J, Xu Y, Liu J; et al. (2024). "Global Burden of Lung Cancer in 2022 and Projections to 2050: Incidence and Mortality Estimates From GLOBOCAN". Cancer Epidemiol. 93: 102693. doi:10.1016/j.canep.2024.102693.
- ↑ Freihat O, Aamir M, Cselik Z, Kovacs A, Sipos D (2026). "Global lung cancer burden, trends, and projections from 2010 to 2050: A population-level severity framework integrating DALYs-per-case and mortality-to-incidence ratio". PLoS One. 21 (7): e0354350. doi:10.1371/journal.pone.0354350.
- ↑ Kratzer TB, Bandi P, Freedman ND; et al. (2024). "Lung Cancer Statistics, 2023". Cancer. 130 (8): 1330–1348. doi:10.1002/cncr.35128.
- ↑ 8.0 8.1 Wolf AMD, Oeffinger KC, Shih TY; et al. (2024). "Screening for Lung Cancer: 2023 Guideline Update From the American Cancer Society". CA Cancer J Clin. 74 (1): 50–81. doi:10.3322/caac.21811.
- ↑ 9.0 9.1 9.2 9.3 9.4 Alberg AJ, Brock MV, Ford JG, Samet JM, Spivack SD (2013). "Epidemiology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines". Chest. 143 (5 Suppl): e1S–e29S. doi:10.1378/chest.12-2345. PMID 23649439.
- ↑ 10.0 10.1 10.2 10.3 10.4 Leiter A, Veluswamy RR, Wisnivesky JP (2023). "The global burden of lung cancer: current status and future trends". Nat Rev Clin Oncol. 20 (9): 624–639. doi:10.1038/s41571-023-00798-3.
- ↑ 11.0 11.1 11.2 Lung Cancer Screening. National Comprehensive Cancer Network. Updated 2026-10-02.
- ↑ 12.0 12.1 Dai X, Bazaco MC, Wang Y; et al. (2022). "Burden of Proof: A Comprehensive Review of the Evidence on the Causal Association Between Tobacco Smoking and Lung Cancer". Nat Med. 28 (10): 2040–2049. doi:10.1038/s41591-022-02013-9. PMID 36216934 Check
|pmid=value (help). - ↑ 13.0 13.1 13.2 13.3 Murphy C, Pandya T, Swanton C, Solomon BJ (2025). "Lung Cancer in Nonsmoking Individuals: A Review". JAMA. 334 (20): 1836–1845. doi:10.1001/jama.2025.17695.
- ↑ 14.0 14.1 LoPiccolo J, Gusev A, Christiani DC, Janne PA (2024). "Lung cancer in patients who have never smoked — an emerging disease". Nat Rev Clin Oncol. 21 (2): 121–146. doi:10.1038/s41571-023-00840-4. PMID 38195910 Check
|pmid=value (help). - ↑ Hendriks LEL, Remon J, Faivre-Finn C; et al. (2024). "Non-small-cell lung cancer". Nat Rev Dis Primers. 10 (1): 71. doi:10.1038/s41572-024-00551-9.