TY - JOUR
T1 - p53 mutations in non-small-cell lung cancers occurring in individuals without a past history of active smoking
AU - Takagi, Y.
AU - Osada, H.
AU - Kuroishi, T.
AU - Mitsudomi, T.
AU - Kondo, M.
AU - Niimi, T.
AU - Saji, S.
AU - Gazdar, A. F.
AU - Takahashi, T.
AU - Minna, J. D.
AU - Takahashi, T.
N1 - Funding Information:
We would like to thank K Kunishima and M Kajita for their help in collecting tumour specimens and clinical data. We are also grateful to S Tominaga for his valuable comments. This work was supported in part by a grant-in-aid for the Second Term Comprehensive Ten-Year Strategy for Cancer Control and grants- in-aid for Cancer Research from the Ministry of Health and Welfare, Japan; by a grant-in-aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture, Japan; and by a grant from the Vehicle Racing Commemorative Foundation.
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
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U2 - 10.1038/bjc.1998.258
DO - 10.1038/bjc.1998.258
M3 - Article
C2 - 9635830
AN - SCOPUS:7144261700
SN - 0007-0920
VL - 77
SP - 1568
EP - 1572
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 10
ER -