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Substantial contribution of extrinsic risk factors to cancer development

Author

Listed:
  • Song Wu

    (Stony Brook University
    Stony Brook Cancer Center, Stony Brook University, Health Sciences Center)

  • Scott Powers

    (Stony Brook University
    Stony Brook Cancer Center, Stony Brook University, Health Sciences Center
    Stony Brook University, Health Sciences Center)

  • Wei Zhu

    (Stony Brook University
    Stony Brook Cancer Center, Stony Brook University, Health Sciences Center)

  • Yusuf A. Hannun

    (Stony Brook Cancer Center, Stony Brook University, Health Sciences Center
    Stony Brook University, Health Sciences Center
    Stony Brook University, Health Sciences Center
    Stony Brook University, Health Sciences Center)

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.

Suggested Citation

  • Song Wu & Scott Powers & Wei Zhu & Yusuf A. Hannun, 2016. "Substantial contribution of extrinsic risk factors to cancer development," Nature, Nature, vol. 529(7584), pages 43-47, January.
    • Handle: RePEc:nat:nature:v:529:y:2016:i:7584:d:10.1038_nature16166
    DOI: 10.1038/nature16166
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    Cited by:

    1. Pingting Ying & Can Chen & Zequn Lu & Shuoni Chen & Ming Zhang & Yimin Cai & Fuwei Zhang & Jinyu Huang & Linyun Fan & Caibo Ning & Yanmin Li & Wenzhuo Wang & Hui Geng & Yizhuo Liu & Wen Tian & Zhiyong, 2023. "Genome-wide enhancer-gene regulatory maps link causal variants to target genes underlying human cancer risk," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Lan Wang & Wenyao Sun & Kaichen Zhou & Minlu Zhang & Pingping Bao, 2019. "Spatial Analysis of Built Environment Risk for Respiratory Health and Its Implication for Urban Planning: A Case Study of Shanghai," IJERPH, MDPI, vol. 16(8), pages 1-16, April.
    3. Tianyu Zhu & Huige Tong & Zhaozhen Du & Stephan Beck & Andrew E. Teschendorff, 2024. "An improved epigenetic counter to track mitotic age in normal and precancerous tissues," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Zvi Safra & Sinong Ma & Tigran Melkonyan, 2019. "Is Allocation Affected by the Perception of Others' Irresponsible Behavior and by Ambiguity?," Risk Analysis, John Wiley & Sons, vol. 39(10), pages 2182-2196, October.
    5. Xi-Zhang Shan & Yong Li & Kun Lai, 2019. "From End Treatment to Source Prevention: Socio-Ecological Approaches to Promote Research on the Environment and Non-Communicable Chronic Diseases with Special Reference to China," IJERPH, MDPI, vol. 16(11), pages 1-8, May.

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