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

Abstract

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. © 2008 Japanese Cancer Association.