Etiologic value of p53 mutation spectra and differences with histology in lung cancers

A total of 297 resected Japanese non-small cell lung cancers (74 squamous cell carcinomas and 223 adenocarcinomas) were analyzed to evaluate the validity of the p53 mutation spectrum as a fingerprint for mutagenic substances as etiological factors. Frequencies of G-->T transversions in smokers were significantly higher than in non-smokers (P = 0.003) and the average incidence of G-->T at hot spot codons of adduct formation was higher than that in other codons in smokers and in the hot spots in non-smokers. Further, the mutation showed a marked strand bias. G-->A transitions at CpG sites (CpG-->CpA) were equally distributed in smokers and non-smokers, and on both strands. A-->G transitions did not show any variation with smoking status in terms of frequency, but exhibited a marked strand bias. Taken together, the G-->T may be a fingerprint of direct mutagenic action of tobacco-related compounds, the A-->G being a new marker for other environmental chemicals, while the CpG-->CpA may be attributable to endogenous spontaneous mutation, for active in lung carcinogenesis.