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Have environmental mutagens caused oncomutations in people?

Nature Genetics volume 34, pages 255–259 (2003)Cite this article

Abstract

Age-specific cancer rates show large historical increases that indict environmental risk factors. But these environmental factors did not necessarily act by increasing oncomutation rates. Mathematical analyses suggest selective effects on pre-existing oncomutants. The widely held hypothesis that environmental chemicals induce a substantial fraction of human point mutations has not been supported by observation. Direct measurement of the kinds and numbers of point mutations in human tissues have, in fact, found no clear relationship with exposure to environmental agents, save for sunlight in the skin. Alternative hypotheses that point mutations arise primarily as errors during turnover of undamaged DNA and that environmental conditions select rather than induce oncomutants seem to better explain the facts of environmental carcinogenesis in humans.

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Figure 1: History (1921–1997) of age-specific mortality from all leukemias, OBS(t), in European-American males grouped by birth decade, 1800–1809 through 1980–1989.

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Acknowledgements

The author wishes to acknowledge the assistance of dozens of colleagues and students in honing the arguments presented herein, especially K. Hemminki, S. Morgenthaler, L. Ehrenberg, D. Brash, P. Hanawalt, A. Morley and E. Gostjeva.

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  1. The author is in the Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    William G Thilly

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Thilly, W. Have environmental mutagens caused oncomutations in people?. Nat Genet 34, 255–259 (2003). https://doi.org/10.1038/ng1205

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