Hernandez-Boussard T M, Hainaut P
International Agency for Research on Cancer, Lyon, France.
Environ Health Perspect. 1998 Jul;106(7):385-91. doi: 10.1289/ehp.98106385.
Mutations in the p53 gene are common in lung cancer. Using data from the the International Agency for Research on Cancer p53 mutation database (R1), we have analyzed the distribution and nature of p53 mutations in 876 lung tumors described in the literature. These analyses confirm that G to T transitions are the predominant type of p53 mutation in lung cancer from smokers. The most frequently mutated codons include 157, 158, 179, 248, 249, and 273, and several of them (157, 248, and 273) have been shown to correspond to sites of in vitro DNA adduct formation 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 these codons in other cancers reported in the database. Thus, lung cancer from smokers shows a distinct, unique p53 mutation spectrum that is not observed in lung cancer from nonsmokers. These results further strengthen the association between active smoking, exposure to PAHs, and lung cancer. They also indicate that a different pattern of mutations occurs in nonsmokers, and this observation may help to identify other agents causally involved in lung cancer in nonsmokers.
p53基因的突变在肺癌中很常见。利用国际癌症研究机构p53突变数据库（R1）的数据，我们分析了文献中描述的876例肺肿瘤中p53突变的分布和性质。这些分析证实，从吸烟者的肺癌中，G到T的转换是p53突变的主要类型。最常发生突变的密码子包括157、158、179、248、249和273，其中几个密码子（157、248和273）已被证明对应于多环芳烃（PAHs）如苯并（a）芘的代谢产物在体外形成DNA加合物的位点。此外，肺癌中密码子248、249和273处的大多数碱基变化与数据库中报道的其他癌症中这些密码子常见的碱基变化不同。因此，吸烟者的肺癌表现出一种独特的、在不吸烟者的肺癌中未观察到的p53突变谱。这些结果进一步加强了主动吸烟、接触PAHs与肺癌之间的关联。它们还表明，不吸烟者中发生了不同的突变模式，这一观察结果可能有助于识别其他与不吸烟者肺癌有因果关系的因素。
