P53 MUTATIONS IN NON-SMALL-CELL LUNG CANCERS OCCURRING IN INDIVIDUALSWITHOUT A PAST HISTORY OF ACTIVE SMOKING

Accumulating evidence suggests that the p53 gene is a good target for molecular epidemiological studies. We previously reported an associati on between the presence of p53 mutations and lifetime cigarette consum ption, Although over 675 p53 mutations have been reported in lung canc ers in the literature thus Tar, 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 c ancer specimens from individuals without any history of active smoking and identified p53 mutations in 26% of the cases, Statistical analysi s of the present cohort of non-smokers also showed absence of signific ant relationship between p53 mutations and age, sex, histological type or disease stage. Comparison of mutational spectra between the presen t results in non-smokers and previously reported mutations in smokers clearly demonstrated G:C to 7: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 G: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 mutati ons,suggesting that these mutations can occur relatively frequently in the absence of active smoking. This study is, to our knowledge, the l argest so far analysing a well-defined cohort of non-smokers in a sing le laboratory.