title: 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.
authors.affiliation: Laboratory of Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi, Yokohama, Kanagawa 241-0815, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Shimmyo
authors.forename: Akira
authors.initials: A
authors.lastname: Okada
authors.forename: Takehisa
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Youhei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Ken
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Osada
authors.forename: Eiju
authors.initials: E
authors.lastname: Tsuchiya
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012907:Smoking / Q000009:adverse effects; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53