» Articles » PMID: 36341427

Association of Smoking Status with Non-small Cell Lung Cancer Patients Harboring Uncommon Epidermal Growth Factor Receptor Mutation

Abstract

Introduction: Uncommon epidermal growth factor receptor (EGFR) mutations include single and complex mutations. However, the association of the smoking status of patients with uncommon and complex mutations remains unclear.

Methods: This retrospective study evaluates the spectrum of uncommon mutations and investigates the influence of smoking status on the frequency of various uncommon mutations using a multi-institutional medical database.

Results: Between 2010 and 2019, 5,608 non-small cell lung cancer (NSCLC) patients were analyzed. mutations were detected in 3,155 (56.3%) patients. Among the 399 (12.6%) patients with uncommon mutations, 198 had single uncommon and 201 complex mutations, including 87 exon 20 insertions, 79 T790M, 70 complex common, and 52 complex uncommon mutations. For comparison, we also included 402 patients with common mutations. The percentage of ever-smokers was significantly higher in patients with uncommon mutations than in patients with common mutations (25.8% vs. 17.4%, = 0.005). Furthermore, the percentage of ever-smokers was higher in those with a complex mutation than in those with a single uncommon mutation (30.3% vs. 21.2%, = 0.040). Among patients carrying uncommon mutations, ever-smokers had significantly more complex uncommon mutations than never-smokers (22.3% vs. 9.8%, = 0.002). Among patients carrying G719X, L861Q, and S768I, ever-smokers tended to have complex mutations more frequently than never-smokers (64.7% vs. 28.7%, 50.0% vs. 18.7%, 88.9% vs. 81.2%, respectively).

Conclusions: Our study demonstrates not only a comprehensive spectrum of uncommon mutations, but also a positive relationship between smoking status and uncommon mutation frequency, especially complex uncommon mutations. The results suggest that smoking contributes to the development of complex mutations.

Citing Articles

Immunotherapy and PD-L1 Tumor Expression in Moroccan Non-Small Cell Lung Cancer Patients with Various Metastasis.

Aazzane O, Fathi S, Charkaoui M, Acharki A, Sahraoui S, Benchakroun N Asian Pac J Cancer Prev. 2024; 25(8):2841-2852.

PMID: 39205582 PMC: 11495451. DOI: 10.31557/APJCP.2024.25.8.2841.


Clinicopathological and prognostic implications of EGFR mutations subtypes in Moroccan non-small cell lung cancer patients: A first report.

Boukansa S, Mouhrach I, Agy F, El Bardai S, Bouguenouch L, Serraj M PLoS One. 2024; 19(6):e0298721.

PMID: 38837980 PMC: 11152259. DOI: 10.1371/journal.pone.0298721.


Targeted therapeutic options in early and metastatic NSCLC-overview.

Galffy G, Morocz E, Korompay R, Hecz R, Bujdoso R, Puskas R Pathol Oncol Res. 2024; 30:1611715.

PMID: 38605928 PMC: 11006988. DOI: 10.3389/pore.2024.1611715.


Association between cigarette smoking history, metabolic phenotypes, and mutation status in patients with non-small cell lung cancer.

Zhang X, Guo X, Gao Q, Zhang J, Zheng J, Zhao G J Thorac Dis. 2023; 15(10):5689-5699.

PMID: 37969305 PMC: 10636471. DOI: 10.21037/jtd-23-1371.


Afatinib overcoming resistance to icotinib and osimertinib in NSCLC with leptomeningeal metastasis in patients with acquired EGFR L858R/T790M or L858R/S768I mutations: Two case reports.

Li G, Fang M, Zhou Y, Liu X, Tian P, Mei F Heliyon. 2023; 9(10):e20690.

PMID: 37860534 PMC: 10582297. DOI: 10.1016/j.heliyon.2023.e20690.


References
1.
Alexandrov L, Ju Y, Haase K, Van Loo P, Martincorena I, Nik-Zainal S . Mutational signatures associated with tobacco smoking in human cancer. Science. 2016; 354(6312):618-622. PMC: 6141049. DOI: 10.1126/science.aag0299. View

2.
Attili I, Passaro A, Pisapia P, Malapelle U, de Marinis F . Uncommon Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence. Curr Oncol. 2022; 29(1):255-266. PMC: 8774526. DOI: 10.3390/curroncol29010024. View

3.
Chiu C, Yang C, Shih J, Huang M, Su W, Lai R . Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment Response in Advanced Lung Adenocarcinomas with G719X/L861Q/S768I Mutations. J Thorac Oncol. 2015; 10(5):793-799. DOI: 10.1097/JTO.0000000000000504. View

4.
Zhang B, Wang S, Qian J, Yang W, Qian F, Lu J . Complex epidermal growth factor receptor mutations and their responses to tyrosine kinase inhibitors in previously untreated advanced lung adenocarcinomas. Cancer. 2018; 124(11):2399-2406. DOI: 10.1002/cncr.31329. View

5.
Graham R, Treece A, Lindeman N, Vasalos P, Shan M, Jennings L . Worldwide Frequency of Commonly Detected EGFR Mutations. Arch Pathol Lab Med. 2017; 142(2):163-167. DOI: 10.5858/arpa.2016-0579-CP. View