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, TP53 mutation patterns show an exceptionally high prevalence of G-->T transversions, mostly occurring at codons demonstrated to be sites of adduction of metabolites of polycyclic aromatic hydrocarbons such as benzo[a]pyrene, one 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 status between successive releases of the IARC TP53 mutation database and that no statistically significant differences could be found in G-->T transversion 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 confirm the existence of a highly significant difference in the prevalence of G-->T transversions between smoking and non-smoking lung cancer patients.