KRAS and lung cancer: We found that NNK exposure was not sufficient to mimic the known human tobacco-associated genetic signatures in lung cancer (i.e., Signatures 4 and 5, ref. 22), which are likely dominated by benzopyrene, but was highly reflective of an alkylating signature consistent with the chemical attack of NNK on DNA (Signature 11) and induced the most frequent tobacco-associated alterations, including Kras and Trp53. This is not surprising as the complex mixture found in tobacco smoke may initiate other mutational processes beyond that of NNK.