Substantial contribution of extrinsic risk factors to cancer development

Wu, S., Powers, S., Zhu, W., Hannun, Y. A. (January 2016) Substantial contribution of extrinsic risk factors to cancer development. Nature, 529 (7584). pp. 43-7. ISSN 0028-0836

DOI: 10.1038/nature16166


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.

Item Type: Paper
Uncontrolled Keywords: *Cell Self Renewal Cell Transformation, Neoplastic/pathology Disease Progression Humans *Models, Biological Mutagenesis/genetics Mutation Accumulation Neoplasms/epidemiology/genetics/*pathology/*prevention & control Organ Specificity Reproducibility of Results Risk Assessment Stem Cells/*cytology/pathology
Subjects: diseases & disorders > cancer
CSHL Authors:
Communities: CSHL Cancer Center Program > Cancer Genetics
CSHL labs > Powers lab
CSHL Cancer Center Program > Cancer Genetics and Genomics Program
Depositing User: Matt Covey
Date: 7 January 2016
Date Deposited: 06 Mar 2018 21:48
Last Modified: 05 Nov 2020 20:55
PMCID: PMC4836858
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