Article | Published:

Substantial contribution of extrinsic risk factors to cancer development

Nature volume 529, pages 4347 (07 January 2016) | Download Citation

Abstract

Recent research has highlighted a strong correlation between tissue-specific cancer risk and the lifetime number of tissue-specific stem-cell divisions. Whether such correlation implies a high unavoidable intrinsic cancer risk has become a key public health debate with the dissemination of the ‘bad luck’ hypothesis. Here we provide evidence that intrinsic risk factors contribute only modestly (less than ~10–30% of lifetime risk) to cancer development. First, we demonstrate that the correlation between stem-cell division and cancer risk does not distinguish between the effects of intrinsic and extrinsic factors. We then show that intrinsic risk is better estimated by the lower bound risk controlling for total stem-cell divisions. Finally, we show that the rates of endogenous mutation accumulation by intrinsic processes are not sufficient to account for the observed cancer risks. Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors. These results are important for strategizing cancer prevention, research and public health.

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Acknowledgements

We thank L. Obeid for constructive comments. This work was supported in part by NCI grants 97132 and 168409 and Stony Brook NYSTEM award C026716.

Author information

Affiliations

  1. Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York 11794, USA

    • Song Wu
    • , Scott Powers
    •  & Wei Zhu
  2. Stony Brook Cancer Center, Stony Brook University, Health Sciences Center, Stony Brook, New York 11794, USA

    • Song Wu
    • , Scott Powers
    • , Wei Zhu
    •  & Yusuf A. Hannun
  3. Department of Pathology, Stony Brook University, Health Sciences Center, Stony Brook, New York 11794, USA

    • Scott Powers
    •  & Yusuf A. Hannun
  4. Department of Medicine, Stony Brook University, Health Sciences Center, Stony Brook, New York 11794, USA

    • Yusuf A. Hannun
  5. Department of Biochemistry, Stony Brook University, Health Sciences Center, Stony Brook, New York 11794, USA

    • Yusuf A. Hannun

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Contributions

Y.A.H. formulated the hypothesis. S.W. and Y.A.H. designed the research. S.W. and W.Z. performed mathematical and statistical analysis. S.W., S.P., W.Z. and Y.A.H. performed research. S.W., S.P., W.Z. and Y.A.H. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Song Wu or Yusuf A. Hannun.

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https://doi.org/10.1038/nature16166

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