A SPECIFIC SPECTRUM OF P53 MUTATIONS IN LUNG-CANCER FROM SMOKERS - REVIEW OF MUTATIONS COMPILED IN THE IARC P53 DATABASE

Mutations in the p53 gene are common in lung cancer. Using data from t he the International Agency for Research an Cancer p53 mutation databa se (R1), we have analyzed the distribution and nature of p53 mutations in 876 lung tumors described in the literature. These analyses confir m that G to T transitions are the predominant type of p53 mutation in lung cancer from smokers. The most frequently mutated codons include 1 57, 158, 179, 248, 249, and 273, and several of them (157, 248, and 27 3) have been shown to correspond to sites of in vitro DNA adduct forma tion by metabolites of polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene. Furthermore, most of the base changes at codons 248, 249, and 273 in lung cancer differ from those commonly observed at the se codons in other cancers reported in the database. Thus, lung cancer from smokers shows a distinct, unique p53 mutation spectrum that is n ot observed in lung cancer from nonsmokers. These results further stre ngthen the association between active smoking, exposure to PAHs, and l ung cancer. They also indicate that a different pattern of mutations o ccurs in nonsmokers, and this observation may help to identify other a gents causally involved in lung cancer in nonsmokers.