Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma Journal Article
| 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. |
| Article Title: | Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma |
| Abstract: | 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 smokingrelated (G→Tor 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. © 2008 American Association for Cancer Research. |
| Keywords: | controlled study; oncoprotein; gene mutation; major clinical study; genetics; mutation; proto-oncogene proteins; cigarette smoking; adenocarcinoma; lung neoplasms; genetic association; gene frequency; smoking; lung tumor; lung adenocarcinoma; ras protein; ras proteins; codon; k ras protein; kras protein, human |
| Journal Title: | Clinical Cancer Research |
| Volume: | 14 |
| Issue: | 18 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2008-09-15 |
| Start Page: | 5731 |
| End Page: | 5734 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-08-0646 |
| PUBMED: | 18794081 |
| PROVIDER: | scopus |
| PMCID: | PMC2754127 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 77" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus" |
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