TP53 mutation spectrum in lung cancers and mutagenic signature of components of tobacco smoke: lessons from the IARC TP53 mutation database

A database of all published TP53 mutations in human cancer is maintained at the International Agency for Research on Cancer (IARC). In lung cancers, T P53 mutation patterns show an exceptionally high prevalence of G-->T transv ersions, mostly occurring at codons demonstrated to be sites of adduction o f metabolites of polycyclic aromatic hydrocarbons such as benzo[a]pyrene, o ne of the major carcinogens of tobacco smoke. These observations have been challenged in a recent 'Discussion Forum' by T.Paschke, who claimed that a large number of discrepancies existed in the classification of smoking stat us between successive releases of the IARC TP53 mutation database and that no statistically significant differences could be found in G-->T transversi on frequencies between smoking and non-smoking lung cancer patients. In the present Letter we question the methods and the conclusions of the analysis presented by Paschke. Based on an assessment of all published data, we con firm the existence of a highly significant difference in the prevalence of G-->T transversions between smoking and non-smoking lung cancer patients.