Toward mutational epidemiology: using mutational signatures of environmental exposures to assess cancer risk.

Exposure to environmental mutagens increases cancer risk, yet exposure-detection methods often lack standardization and sensitivity. Genotoxic agents leave characteristic 'mutational signatures' in DNA, creating permanent, quantitative records of past exposures. Analyses of these signatures have clarified the mutational impacts of many established carcinogens and implicated contributions of previously unrecognized ones. Recent studies indicate that signatures of environmental exposures may be detectable in readily accessible human tissues, providing a basis for population-scale monitoring-termed 'mutational epidemiology'-which could complement conventional approaches to refine and accelerate the identification of mutagenic carcinogens. Realizing this potential will require identifying accessible tissues that capture mutations from specific exposure types and routes, defining signature profiles within those tissues, and determining how well they reflect mutagenesis in cancer-prone organs.