This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gealy, R. Articles by Keohavong, P. Search for Related Content PubMed PubMed Citation Articles by Gealy, R. Articles by Keohavong, P.

Comparison of Mutations in the p53 and K-ras Genes in Lung Carcinomas from Smoking and Nonsmoking Women¹

Departments of Environmental and Occupational Health [R. G., L. Z., P. K.], Pharmacology [J. M. S.], and Surgery [J. D. L.], University of Pittsburgh, and Lung Cancer Basic Research Program, University of Pittsburgh Cancer Institute [P. K., J. M. S., J. D. L.], Pittsburgh, Pennsylvania 15261

Lung cancer incidence is increasing in women with little or no tobacco exposure, and the cause of this trend is not known. One possibility is increased sensitivity to environmental tobacco smoke in women nonsmokers diagnosed with lung cancer. To determine whether mutations associated with tobacco exposure are found in the lung tumors of women who are lifetime nonsmokers or occasional smokers, we compared the p53 and K-ras mutational spectra in lung carcinomas from 23 female nonsmokers, 2 female occasional smokers (<10 pack-years), and 30 female long-term smokers (20–100 pack-years). We also looked for p53 and K-ras mutations in three carcinoid lung tumors, two from female nonsmokers and one from a female occasional smoker. For the p53 gene, exons 4–8 were examined for mutations; for the K-ras gene, exon 1 was examined. No mutations were found in the carcinoid tumors. In lung carcinomas, p53 mutations were identified in six (26.1%) of the cases from lifetime nonsmokers and consisted of five transitions (including three C to T, one G to A, and one T to C) and one T to A transversion. In comparison, p53 mutations were identified in 10 (31.3%) of the 32 lung carcinomas from short-term and long-term smokers and consisted of six transversions (four G to T, one A to T, and one G to C), one A to G transition, one C to T transition, and two deletions of one to four bp. Mutations in the p53 gene found in nonsmokers also occurred in either different codons or different positions within a codon compared with those seen in long-term smokers. K-ras mutations in codon 12 were identified in two lung carcinomas (8.7%) from lifetime nonsmokers. The K-ras mutations found were a G to T transversion and a G to A transition. Eight (25%) of the 32 lung carcinomas from smokers contained K-ras mutations in codons 12 and 13 (four G to T transversions and four G to A transitions). In addition, six silent mutations that are most likely polymorphisms were found in both smokers and nonsmokers. These results confirm that K-ras mutations are more frequent in smokers than in nonsmokers, but that the same type of mutation in the K-ras gene is found in both groups. In contrast, although the frequency of mutation in the p53 gene was similar in lifetime nonsmokers compared with long-term smokers, the types and spectra of mutation are significantly different. Two of the C to T transitions found in nonsmokers, but none of those found in smokers, occur at the C of a CpG site. These results suggest the mutagen(s) and/or mechanisms of p53 mutations in women nonsmokers are different from those responsible for p53 mutations in women smokers, which are probably largely induced by tobacco mutagens.

This article has been cited by other articles:

				I.A. Lea, M.A. Jackson, X. Li, S. Bailey, S.D. Peddada, and J.K. Dunnick Genetic pathways and mutation profiles of human cancers: site- and exposure-specific patterns Carcinogenesis, September 1, 2007; 28(9): 1851 - 1858. [Abstract] [Full Text] [PDF]

				C.-K. Toh and W.-T. Lim Lung cancer in never-smokers J. Clin. Pathol., April 1, 2007; 60(4): 337 - 340. [Full Text] [PDF]

				J. Subramanian and R. Govindan Lung Cancer in Never Smokers: A Review J. Clin. Oncol., February 10, 2007; 25(5): 561 - 570. [Abstract] [Full Text] [PDF]

				Y. E. Miller Pathogenesis of Lung Cancer: 100 Year Report Am. J. Respir. Cell Mol. Biol., September 1, 2005; 33(3): 216 - 223. [Abstract] [Full Text] [PDF]

				F. Le Calvez, A. Mukeria, J. D. Hunt, O. Kelm, R. J. Hung, P. Taniere, P. Brennan, P. Boffetta, D. G. Zaridze, and P. Hainaut TP53 and KRAS Mutation Load and Types in Lung Cancers in Relation to Tobacco Smoke: Distinct Patterns in Never, Former, and Current Smokers Cancer Res., June 15, 2005; 65(12): 5076 - 5083. [Abstract] [Full Text] [PDF]

				H. Shigematsu, L. Lin, T. Takahashi, M. Nomura, M. Suzuki, I. I. Wistuba, K. M. Fong, H. Lee, S. Toyooka, N. Shimizu, et al. Clinical and Biological Features Associated With Epidermal Growth Factor Receptor Gene Mutations in Lung Cancers J Natl Cancer Inst, March 2, 2005; 97(5): 339 - 346. [Abstract] [Full Text] [PDF]

				C.-K. Toh, E.-H. Wong, W.-T. Lim, S.-S. Leong, K.-W. Fong, J. Wee, and E.-H. Tan The Impact of Smoking Status on the Behavior and Survival Outcome of Patients With Advanced Non-small Cell Lung Cancer: A Retrospective Analysis Chest, December 1, 2004; 126(6): 1750 - 1756. [Abstract] [Full Text] [PDF]

				D. M. DeMarini, S. Landi, D. Tian, N. M. Hanley, X. Li, F. Hu, B. C. Roop, M. J. Mass, P. Keohavong, W. Gao, et al. Lung Tumor KRAS and TP53 Mutations in Nonsmokers Reflect Exposure to PAH-Rich Coal Combustion Emissions Cancer Res., September 1, 2001; 61(18): 6679 - 6681. [Abstract] [Full Text] [PDF]

				K. H. Vahakangas, W. P. Bennett, K. Castren, J. A. Welsh, M. A. Khan, B. Blomeke, M. C. R. Alavanja, and C. C. Harris p53 and K-ras Mutations in Lung Cancers from Former and Never-Smoking Women Cancer Res., June 1, 2001; 61(11): 4350 - 4356. [Abstract] [Full Text] [PDF]

				P. Hainaut and G. P. Pfeifer Patterns of p53 G{->}T transversions in lung cancers reflect the primary mutagenic signature of DNA-damage by tobacco smoke Carcinogenesis, March 1, 2001; 22(3): 367 - 374. [Abstract] [Full Text] [PDF]

				M.J. Lafuente, X. Casterad, M. Trias, C. Ascaso, R. Molina, A. Ballesta, S. Zheng, J.K. Wiencke, and A. Lafuente NAD(P)H:quinone oxidoreductase-dependent risk for colorectal cancer and its association with the presence of K-ras mutations in tumors Carcinogenesis, October 1, 2000; 21(10): 1813 - 1819. [Abstract] [Full Text] [PDF]

				K. Husgafvel-Pursiainen, P. Boffetta, A. Kannio, F. Nyberg, G. Pershagen, A. Mukeria, V. Constantinescu, C. Fortes, and S. Benhamou p53 Mutations and Exposure to Environmental Tobacco Smoke in a Multicenter Study on Lung Cancer Cancer Res., June 1, 2000; 60(11): 2906 - 2911. [Abstract] [Full Text] [PDF]