Striking Surge in Lung Cancer Incidence in Children of Early Life

Abstract

Lung cancer ranks first in mortality and the third in total cancer cases diagnosed in the US. The epidemiological trends may vary among different age groups, while the dynamics of risk factors evolve as well. We aim to carefully characterize trends of lung cancer among different age groups in the past two decades, by accessing the Surveillance, Epidemiology, and End Results (SEER) datasets from the National Cancer Institute (NCI), and to delineate possible root causes. The SEER datasets were obtained from NCI. Data on environmental risk factors were acquired from the Environmental Protection Agency and the United States Geological Survey. The tobacco consumption data were sourced from the Centers for Disease Control and Prevention. Trends were examined statistically with the Mann-Kendall algorithm. The incidence rate of lung cancer in the <15 age group has been rising in the past two decades, most strikingly among infants in the 0 age group (at birth to less than 1 year old). These findings were unique for lung cancer. The usage of e-Cigarettes among pregnant women increased, while the potential influence of other known risk factors was on the decline. A shrinkage of the infant population and a higher rate of pregnancy loss were observed during the same timespan. A striking rise in lung cancer incidence among infants has been identified that is opposite to the declining trend in the overall population, which might be related to increased e-Cigarette use in pregnant women. Urgent further investigation is warranted to safeguard the newborn population from being continuously affected potentially by lung cancer.

Keywords

Lung cancer / Newborns / e-Cigarette / Vaping / Pregnant women / Miscarriage / Tobacco / Radon gas

Author Contributions

Conceptualization, H.C.; Methodology, N.C.Z., J.J., H.L., H.C.; Validation, N.C.Z., H.C.; Formal Analysis, N.C.Z., J.J., H.L., H.C.; Data Curation, N.C.Z., J.J., H.L., H.C.; Writing-Original Draft Preparation, N.C.Z., J.J., H.L., H.C.; Writing-Review & Editing, N.C.Z., H.C.; Supervision, H.C.; Project Administration, H.C.; Funding Acquisition, H.C.

Ethics Statement

The studies followed standard protocols to assess publicly available datasets.

Informed Consent Statement

Patient consent was waived due to access of publicly available datasets.

Data Availability Statement

All of the data presented in the article are available upon reasonable requests.

Funding

This work was supported by National Institute of Health National Heart, Lung and Blood Institute (NHLBI) awards HL142951 (to H.C.), HL154754 (to H.C.) and HL162407 (to H.C.).

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References

[1] SEER*Explorer: An Interactive Website for SEER Cancer Statistics. Surveillance Research Program, National Cancer Institute. 17 April 2024. [updated: 27 June 2024; cited 17 July 2024]. (Data Source(s): SEER Incidence Data, November 2023 Submission (1975-2021), SEER 22 registries). Available online: https://seer.cancer.gov/statistics-network/explorer/ (accessed on 17 July 2024).

[2] WHO. International Agency for Research on Cancer. Global Cancer Observatory: Cancer Today. Available online: https://gco.iarc.fr/today (accessed on 19 February 2025).

[3] Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS. Lung cancer. Lancet 2021, 398, 535-554. DOI: 10.1016/S0140-6736(21)00312-3

[4] Cancer Facts and Figures 2023. American Cancer Society. Available online: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023-cancer-facts-and-figures.pdf (accessed on 2 February 2025).

[5] USGS. Mineral Commodity Summaries. US Geological Survey. January 2022. Available online: https://pubs.usgs.gov/periodicals/mcs2021/mcs2021-asbestos.pdf (accessed on 2 February 2025).

[6] Rolle-Lake L, Robbins E. Behavioral Risk Factor Surveillance System ; StatPearls: Treasure Island, FL, USA, 2025.

[7] Martinez GM, Daniels K. Fertility of Men and Women Aged 15-49 in the United States: National Survey of Family Growth, 2015-2019. Natl. Health Stat. Rep. 2023, 179. DOI: 10.15620/cdc:122080

[8] Kendall MG, Gibbons JD. Rank Correlation Methods , 5th ed.; Arnold E, Ed.; Oxford University Press: Oxford, UK, 1990.

[9] NCI. Lung and Bronchus, Recent Trends in SEER Relative Survival Rates, 2000-2022. Available online: https://seer.cancer.gov/statfacts/html/lungb.html (accessed on 22 April 2025).

[10] Balzer BWR, Loo C, Lewis CR, Trahair TN, Anazodo AC . Adenocarcinoma of the Lung in Childhood and Adolescence: A Systematic Review. J. Thorac. Oncol. 2018, 13, 1832-1841. DOI: 10.1016/j.jtho.2018.08.2020

[11] Borgia P, Cafferata B, Paratore C, Anfigeno L, Conte A, Florio A, et al. Primary Lung Tumors in Children: Insights from a Single-Center Case Series. J. Clin. Med. 2025, 14, 2173. DOI: 10.3390/jcm14072173

[12] Gupta P, Chugh S, Gupta N, Gupta K, Sodhi KS, Kakkar N, et al. Cytomorphologic and immunocytochemical characterization of pediatric pleuropulmonary blastoma with a comprehensive review of the literature. Diagn. Cytopathol. 2024, 52, 103-115. DOI: 10.1002/dc.25254

[13] EPA. Highlights of the Diesel Emissions Reduction Program (2008-2018). In Diesel Emissions Reduction Act (DERA) Fifth Report to Congress; U.S. Environmental Protection Agency (EPA): Washington, DC, USA, 2022.

[14] Li L, Coull BA, Zilli Vieira CL, Koutrakis P. High-resolution national radon maps based on massive indoor measurements in the United States. Proc. Natl. Acad. Sci. USA 2025, 122, e2408084121. DOI: 10.1073/pnas.2408084121

[15] Cai H, Wang C. Graphical review: The redox dark side of e-cigarettes; exposure to oxidants and public health concerns. Redox Biol. 2017, 13, 402-406. DOI: 10.1016/j.redox.2017.05.013

[16] Cai H, Wang C. Surviving with Smog and Smoke: Precision Interventions? Chest 2017, 152, 925-929. DOI: 10.1016/j.chest.2017.06.030

[17] Cai H, Garcia JGN, Wang C. More to Add to E-Cigarette Regulations: Unified Approaches. Chest 2020, 157, 771-773. DOI: 10.1016/j.chest.2019.11.024

[18] Zhang Y, Wang L, Mutlu GM, Cai H. More to Explore: Further Definition of Risk Factors for COPD-Differential Gender Difference, Modest Elevation in PM_2.5, and e-Cigarette Use . Front. Physiol. 2021, 12, 669152. DOI: 10.3389/fphys.2021.669152

[19] Youn JY, Middlekauff HR, Reudiseuli I, Huang K, Cai H. Endothelial damage in young adult e-cigarette users. Redox Biol. 2023, 62, 102688. DOI: 10.1016/j.redox.2023.102688

[20] Zong NC, Zhang Y, Cai H. Keep Gimmicks of Toy E-Cigarettes Away and Juveniles on Track Towards the Tobacco Endgame. Chest 2024, 166, 1293-1295. DOI: 10.1016/j.chest.2024.06.3810

[21] Bracken-Clarke D, Kapoor D, Baird AM, Buchanan PJ, Gately K, Cuffe S, et al. Vaping and lung cancer-A review of current data and recommendations. Lung Cancer 2021, 153, 11-20. DOI: 10.1016/j.lungcan.2020.12.030

[22] Ali FRM, Seidenberg AB, Crane E, Seaman E, Tynan MA, Marynak K. E-cigarette Unit Sales by Product and Flavor Type, and Top-Selling Brands, United States, 2020-2022. MMWR Morb. Mortal. Wkly. Rep. 2023, 72, 672-677. DOI: 10.15585/mmwr.mm7225a1

[23] Wen X, Liu L, Moe AA, Ormond IK, Shuren CC, Scott IN, et al. Use of E-Cigarettes and Cigarettes During Late Pregnancy Among Adolescents. JAMA Netw. Open 2023, 6, e2347407. DOI: 10.1001/jamanetworkopen.2023.47407

[24] Liu B, Xu G, Rong S, Santillan DA, Santillan MK, Snetselaar LG, et al. National Estimates of e-Cigarette Use Among Pregnant and Nonpregnant Women of Reproductive Age in the United States, 2014-2017. JAMA Pediatr. 2019, 173, 600-602. DOI: 10.1001/jamapediatrics.2019.0658

[25] East KA, Hitchman SC, McNeil A, Thrasher JF, Hammond D. Social norms towards smoking and vaping and associations with product use among youth in England, Canada, and the US. Drug Alcohol Depend. 2019, 205, 107635. DOI: 10.1016/j.drugalcdep.2019.107635

[26] Tang MS, Wu XR, Lee HW, Xia Y, Deng FM, Moreira AL, et al. Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice. Proc. Natl. Acad. Sci. USA 2019, 116, 21727-21731. DOI: 10.1073/pnas.1911321116

[27] Aslaner DM, Alghothani O, Saldana TA, Ezell KG, Yallourakis MD, MacKenzie DM, et al. E-cigarette vapor exposure in utero causes long-term pulmonary effects in offspring. Am. J. Physiol. Lung Cell. Mol. Physiol. 2022, 323, L676-L682. DOI: 10.1152/ajplung.00233.2022

[28] Liu Z, Zhang Y, Youn JY, Zhang Y, Makino A, Yuan JX, et al. Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO Bioavailability. Antioxidants 2022, 11, 904. DOI: 10.3390/antiox11050904

[29] Chen H, Li G, Chan YL, Chapman DG, Sukjamnong S, Nguyen T, et al. Maternal E-Cigarette Exposure in Mice Alters DNA Methylation and Lung Cytokine Expression in Offspring. Am. J. Respir. Cell Mol. Biol. 2018, 58, 366-377. DOI: 10.1165/rcmb.2017-0206RC

[30] Noel A, Yilmaz S, Farrow T, Schexnayder M, Eickelberg O, Jelesijevic T. Sex-Specific Alterations of the Lung Transcriptome at Birth in Mouse Offspring Prenatally Exposed to Vanilla-Flavored E-Cigarette Aerosols and Enhanced Susceptibility to Asthma. Int. J. Environ. Res. Public Health 2023, 20, 3710. DOI: 10.3390/ijerph20043710

[31] Ozekin YH, Saal ML, Pineda RH, Moehn K, Ordonez-Erives MA, Delgado Figueroa MF, et al. Intrauterine exposure to nicotine through maternal vaping disrupts embryonic lung and skeletal development via the Kcnj2 potassium channel. Dev. Biol. 2023, 501, 111-123. DOI: 10.1016/j.ydbio.2023.06.002

[32] Noel A, Hansen S, Zaman A, Perveen Z, Pinkston R, Hossain E, et al. In utero exposures to electronic-cigarette aerosols impair the Wnt signaling during mouse lung development. Am. J. Physiol. Lung Cell. Mol. Physiol. 2020, 318, L705-L722. DOI: 10.1152/ajplung.00408.2019

[33] Lin SY, Wang L, Zhou W, Kitsantas P, Wen X, Xue H. E-cigarette use during pregnancy and its association with adverse birth outcomes in the US. Prev. Med. 2023, 166, 107375. DOI: 10.1016/j.ypmed.2022.107375

[34] Schier JG, Meiman JG, Layden J, Mikosz CA, VanFrank B, King BA, et al. Severe Pulmonary Disease Associated with Electronic-Cigarette-Product Use-Interim Guidance. MMWR Morb. Mortal. Wkly. Rep. 2019, 68, 787-790. DOI: 10.15585/mmwr.mm6836e2