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.
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.
Authors: R J Slebos; R E Kibbelaar; O Dalesio; A Kooistra; J Stam; C J Meijer; S S Wagenaar; R G Vanderschueren; N van Zandwijk; W J Mooi Journal: N Engl J Med Date: 1990-08-30 Impact factor: 91.245
Authors: S L Graziano; G P Gamble; N B Newman; L Z Abbott; M Rooney; S Mookherjee; M L Lamb; L J Kohman; B J Poiesz Journal: J Clin Oncol Date: 1999-02 Impact factor: 44.544
Authors: Timothy Winton; Robert Livingston; David Johnson; James Rigas; Michael Johnston; Charles Butts; Yvon Cormier; Glenwood Goss; Richard Inculet; Eric Vallieres; Willard Fry; Drew Bethune; Joseph Ayoub; Keyue Ding; Lesley Seymour; Barbara Graham; Ming-Sound Tsao; David Gandara; Kenneth Kesler; Todd Demmy; Frances Shepherd Journal: N Engl J Med Date: 2005-06-23 Impact factor: 91.245
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Authors: R Rosell; F Molina; I Moreno; E Martínez; A Pifarré; A Font; S Li; Z Skacel; J Gómez-Codina; C Camps Journal: Lung Cancer Date: 1995-04 Impact factor: 5.705
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Authors: L V Sequist; R S Heist; A T Shaw; P Fidias; R Rosovsky; J S Temel; I T Lennes; S Digumarthy; B A Waltman; E Bast; S Tammireddy; L Morrissey; A Muzikansky; S B Goldberg; J Gainor; C L Channick; J C Wain; H Gaissert; D M Donahue; A Muniappan; C Wright; H Willers; D J Mathisen; N C Choi; J Baselga; T J Lynch; L W Ellisen; M Mino-Kenudson; M Lanuti; D R Borger; A J Iafrate; J A Engelman; D Dias-Santagata Journal: Ann Oncol Date: 2011-11-09 Impact factor: 32.976
Authors: J Jack Lee; Lei Feng; Daniel S Reshef; Anita L Sabichi; Brendell Williams; Waree Rinsurongkawong; Ignacio I Wistuba; Reuben Lotan; Scott M Lippman Journal: Cancer Prev Res (Phila) Date: 2010-05-25
Authors: Hua Wang; Matthew B Schabath; Ying Liu; Olya Stringfield; Yoganand Balagurunathan; John J Heine; Steven A Eschrich; Zhaoxiang Ye; Robert J Gillies Journal: Clin Lung Cancer Date: 2015-11-12 Impact factor: 4.785
Authors: Robert C Doebele; Xian Lu; Christopher Sumey; Delee A Maxson; Andrew J Weickhardt; Ana B Oton; Paul A Bunn; Anna E Barón; Wilbur A Franklin; Dara L Aisner; Marileila Varella-Garcia; D Ross Camidge Journal: Cancer Date: 2012-01-26 Impact factor: 6.860