Open AccessEtiologic value of p53 mutation spectra and differences with histology in lung cancers
Author(s) -
Shimmyo Takuo,
Okada Akira,
Hashimoto Takehisa,
Kobayashi Yasuhito,
Miyagi Youhei,
Ishikawa Yuichi,
Nakagawa Ken,
Osada Hiroaki,
Tsuchiya Eiju
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00686.x
Subject(s) - carcinogenesis , lung cancer , mutation , cpg site , biology , lung , cancer research , etiology , cell , cancer , medicine , pathology , genetics , gene , gene expression , dna methylation
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. ( Cancer Sci 2008; 99: 287–295)