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. 2008 Sep 15;14(18):5731-4.
doi: 10.1158/1078-0432.CCR-08-0646.

Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma

Gregory J Riely  1 , Mark G Kris, Daniel Rosenbaum, Jenifer Marks, Allan Li, Dhananjay A Chitale, Khedoudja Nafa, Elyn R Riedel, Meier Hsu, William Pao, Vincent A Miller, Marc Ladanyi
Affiliations

Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma

Gregory J Riely et al. Clin Cancer Res. .

Abstract

Purpose: KRAS mutations are found in approximately 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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Figures

Figure
Figure
Frequency of KRAS mutation by smoking history. Mantel-Haenszel Chi-Square test for trend was used to calculate p-value.
See this image and copyright information in PMC

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