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.
Shimmyo
Takuo
T
Laboratory of Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi, Yokohama, Kanagawa 241-0815, Japan.
Okada
Akira
A
Hashimoto
Takehisa
T
Kobayashi
Yasuhito
Y
Miyagi
Youhei
Y
Ishikawa
Yuichi
Y
Nakagawa
Ken
K
Osada
Hiroaki
H
Tsuchiya
Eiju
E
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*
D016159:Tumor Suppressor Protein p53