Frequency and Distinctive Spectrum of KRAS Mutations in Never Smokers with Lung Adenocarcinoma
Open accessAbstract
Purpose: KRAS mutations are found in ∼25% of lung adenocarcinomas in Western countries and, as a group, have been strongly associated with cigarette smoking. These mutations are predictive of poor prognosis in resected disease as well as resistance to treatment with erlotinib or gefitinib. Experimental Design: We determined the frequency and type of KRAS codon 12 and 13 mutations and characterized their association with cigarette smoking history in patients with lung adenocarcinomas. Results: KRAS mutational analysis was done on 482 lung adenocarcinomas, 81 (17%) of which were obtained from patients who had never smoked cigarettes. KRAS mutations were found in 15% (12 of 81; 95% confidence intervals, 8-24%) of tumors from never smokers. Similarly, 22% (69 of 316; 95% confidence intervals, 17-27%) of tumors from former smokers, and 25% (21 of 85; 95% confidence intervals, 16-35%) of tumors from current smokers had KRAS mutations. The frequency of KRAS mutation was not associated with age, gender, or smoking history. The number of pack years of cigarette smoking did not predict an increased likelihood of KRAS mutations. Never smokers were significantly more likely than former or current smokers to have a transition mutation (G→A) rather than the transversion mutations known to be smoking-related (G→T or G→C; P < 0.0001). Conclusions: Based on our data, KRAS mutations are not rare among never smokers with lung adenocarcinoma and such patients have a distinct KRAS mutation profile. The etiologic and biological heterogeneity of KRAS mutant lung adenocarcinomas is worthy of further study.
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A genomic analysis of KRAS mutations in NSCLC showed that a G>A transition is increasingly seen in never smokers, while a G>T transversion is commonly seen in current and former smokers diagnosed with lung cancer.
“A genomic analysis of KRAS mutations in NSCLC showed that a G>A transition has been increasingly seen in those who have never smoked, while a G>T transversion is commonly seen in current and former smokers who are diagnosed with lung cancer6.”
From Selective KRAS G12C inhibitors in non-small cell lung cancer: chemistry, concurrent pathway alterations, and clinical outcomes (2021) · cites this paper as [6]
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- Authors
- Riely, G. J., Kris, M. G., Rosenbaum, D., Marks, J., Li, A., Chitale, D. A., Nafa, K., Riedel, E. R., Hsu, M., Pao, W., Miller, V. A., & Ladanyi, M.
- Affiliations
- 1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine,
- 2Department of Pathology,
- Memorial Sloan Kettering Cancer Center (US)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2008-09-14
- Volume
- 14
- Issue
- 18
- Pages
- 5731-5734
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC2754127
- OpenAlex
- W1994225895
- Cited by
- 578
- References
- 26
- Citations by year
- 2026: 18 · 2025: 16 · 2024: 39 · 2023: 26 · 2022: 38 · 2021: 28 · 2020: 28 · 2019: 29 · 2018: 28 · 2017: 23 · 2016: 35 · 2015: 42 · 2014: 46 · 2013: 53 · 2012: 35
- FWCI
- 28.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P01CA129243, NIH P01 CA129243)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- KRAS mutation, lung adenocarcinoma, never smokers, cigarette smoking, smoking history, codon 12 and 13 mutations, mutation frequency, pack-years, EGFR tyrosine kinase inhibitor resistance, tumor molecular heterogeneity
- MeSH terms
- Adenocarcinoma, Adult, Aged, Aged, 80 and over, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Proto-Oncogene Proteins, Smoking, Proto-Oncogene Proteins p21(ras), ras Proteins
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