The TP53 gene, tobacco exposure, and lung cancer.

Of the various genetic alterations in lung cancer, the abnormalities of the TP53 gene (p53) are among the most frequent and important events. Because of its importance, many aspects of TP53 have been studied, including preneoplastic lesions and TP53as a marker for early detection and prognosis and as a therapeutic option. We summarize recent knowledge of TP53 in lung cancer with a special emphasis on the relationship between smoking exposure (e.g, cigarette, etc.) and specific mutational pattern of TP53by analyzing the latest version of the International Agency for Research on Cancer (IARC) database on TP53 mutations in human cancer. Our analysis confirmed several other studies showing significant differences in the frequencies of G:C to T:A transversions between ever-smokers and never-smokers. Furthermore, when comparing the mutational spectrum by gender, important differences were noted between male and female never-smokers. We concluded that the previously noted G:C to T:A transversions were mainly due to female smokers having a high frequency of these changes compared to female never-smokers. There was no relationship between adenocarcinomas and squamous cell carcinomas independent of gender. We also examined the seven codons which have been previously identified as hot spots, that is, the sites of frequent G:C to T:A transversions in smoking-related lung cancers. However, there was no specific codon which was strongly related to smoke exposure despite a moderate relationship. We considered the term "warmspot" may be more appropriate. While mutations of TP53 are frequent in lung cancers, further investigation is necessary to understand their role for lung carcinogenesis, especially as they relate to gender differences, and to translate our laboratory knowledge to clinical applications. Copyright 2003 Wiley-Liss, Inc.