Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Dec 1;118(23):5840-7.
doi: 10.1002/cncr.27637. Epub 2012 May 17.

Driver mutations determine survival in smokers and never-smokers with stage IIIB/IV lung adenocarcinomas

Paul K Paik  1 , Melissa L Johnson, Sandra P D'Angelo, Camelia S Sima, Daphne Ang, Snjezana Dogan, Vincent A Miller, Marc Ladanyi, Mark G Kris, Gregory J Riely
Affiliations

Driver mutations determine survival in smokers and never-smokers with stage IIIB/IV lung adenocarcinomas

Paul K Paik et al. Cancer. .

Abstract

Background: The authors previously demonstrated that never-smokers with stage IIIB/IV nonsmall cell lung cancer (NSCLC) lived 50% longer than former/current smokers. This observation persisted after adjusting for age, performance status, and sex. In this study, the authors hypothesized that smoking-dependent differences in the distribution of driver mutations may explain differences in prognosis between these subgroups.

Methods: In total, 293 never-smokers and 382 former/current smokers with lung adenocarcinoma who underwent testing for epidermal growth factor receptor (EGFR) mutations and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and rearrangements in anaplastic lymphoma kinase (ALK) between 2009 and 2010 were investigated. Clinical outcomes and patient characteristics were collected. Survival probabilities were estimated using the Kaplan-Meier method. Group comparison was performed with log-rank tests and Cox proportional hazards methods.

Results: Although the overall incidence of these mutations was nearly identical (55% never-smokers vs 57% current/former smokers; P = .48), there were significant differences in the distribution of mutations between these groups for EGFR mutations (37% never-smokers vs 14% former/current smokers; P < .0001), KRAS mutations (4% never-smokers vs 43% former/current smokers; P < .0001), and ALK rearrangements (12% never-smokers vs 2% former/current smokers; P < .0001). Among never-smokers and former/current smokers, the prognosis differed significantly by genotype. Patients who had KRAS mutations had the poorest survival. Smoking status, however, had no influence on survival within each genotype.

Conclusions: Never-smokers and former/current smokers with lung adenocarcinomas were not homogeneous subgroups. Each was made up of individuals whose tumors had a unique distribution of driver mutations, which were associated with different prognoses, irrespective of smoking history.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Relative frequency of driver mutations in never smokers and former/current smokers with lung adenocarcinoma. Other/uncharacterized denotes patients without a mutation in EGFR or KRAS or rearrangement in ALK. Differences in the frequency of each mutation between never smokers and former/current smokers were significant in all cases (p<0.0001 for all genotypes).
Figure 2
Figure 2
A–C. Overall survival in advanced stage (IIIB/IV) lung adenocarcinoma never smokers and former/current smokers harboring (A) EGFR mutations; (B) KRAS mutations; and (C) ALK rearrangements.
Figure 3
Figure 3
Overall survival in advanced stage (IIIB/IV) lung adenocarcinoma never smokers and former/current smokers with other/uncharacterized genotype.
See this image and copyright information in PMC

References

    1. Kris MG, Natale RB, Herbst RS, et al. Efficacy of Gefitinib, an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Symptomatic Patients With Non-Small Cell Lung Cancer: A Randomized Trial. JAMA. 2003;290(16):2149–2158. - PubMed
    1. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in Previously Treated Non-Small-Cell Lung Cancer. N Engl J Med. 2005;353(2):123–132. - PubMed
    1. Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer) The Lancet. 2005;366(9496):1527–1537. - PubMed
    1. Lynch TJ, Bell DW, Sordella R, et al. Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non-Small-Cell Lung Cancer to Gefitinib. N Engl J Med. 2004;350(21):2129–2139. - PubMed
    1. Paez JG, Janne PA, Lee JC, et al. EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy. Science. 2004;304(5676):1497–1500. - PubMed

Publication types

MeSH terms