p53 mutations in non-small-cell lung cancers occurring in individuals without a past history of active smoking

Y. Takagi, H. Osada, T. Kuroishi, T. Mitsudomi, M. Kondo, T. Niimi, S. Saji, A. F. Gazdar, T. Takahashi, J. D. Minna, T. Takahashi

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Abstract

Accumulating evidence suggests that the p53 gene is a good target for molecular epidemiological studies. We previously reported an association between the presence of p53 mutations and lifetime cigarette consumption. Although over 675 p53 mutations have been reported in lung cancers in the literature thus far, very little is known about the nature of such changes in lung cancers in the absence of a smoking background. In the present study, we therefore analysed 69 non-small-cell lung cancer specimens from individuals without any history of active smoking and identified p53 mutations in 26% of the cases. Statistical analysis of the present cohort of non-smokers also showed absence of significant relationship between p53 mutations and age, sex, histological type or disease stage. Comparison of mutational spectra between the present results in non-smokers and previously reported mutations in smokers clearly demonstrated G:C to T:A transversions to be significantly less frequent in non-smokers than in smokers (OR 5.35, 95% CI 1.77 - 16.12). Interestingly, G:C to C:G and G:C to A:T mutations were also observed in tumours of non-smokers at similar frequencies to G:C to T:A mutations, suggesting that these mutations can occur relatively frequently in the absence of active smoking. This study is, to our knowledge, the largest so far analysing a well-defined cohort of non-smokers in a single laboratory.

Original languageEnglish
Pages (from-to)1568-1572
Number of pages5
JournalBritish Journal of Cancer
Volume77
Issue number10
DOIs
Publication statusPublished - 01-01-1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Takagi, Y., Osada, H., Kuroishi, T., Mitsudomi, T., Kondo, M., Niimi, T., Saji, S., Gazdar, A. F., Takahashi, T., Minna, J. D., & Takahashi, T. (1998). p53 mutations in non-small-cell lung cancers occurring in individuals without a past history of active smoking. British Journal of Cancer, 77(10), 1568-1572. https://doi.org/10.1038/bjc.1998.258