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Developmental reprogramming of cancer susceptibility

A Corrigendum to this article was published on 24 July 2012

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Abstract

Gene–environment interactions have been traditionally understood to promote the acquisition of mutations that drive multistage carcinogenesis, and, in the case of inherited defects in tumour suppressor genes, additional mutations are required for cancer development. However, the developmental origins of health and disease (DOHAD) hypothesis provides an alternative model whereby environmental exposures during development increase susceptibility to cancer in adulthood, not by inducing genetic mutations, but by reprogramming the epigenome. We hypothesize that this epigenetic reprogramming functions as a new type of gene–environment interaction by which environmental exposures target the epigenome to increase cancer susceptibility.

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Figure 1: The thrifty phenotype hypothesis.
Figure 2: Developmental reprogramming dormancy.
Figure 3: Model of the engagement of the epigenetic machinery by environmental oestrogens via non-genomic ER signalling.
Figure 4: Developmental reprogramming of the penetrance of defects in tumour suppressor genes.

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Acknowledgements

C.L.W. is supported by grants from the US National Institutes of Health (ES018789, ES008263 and ES020055) and the Cancer Prevention and Research Institute of Texas (CPRIT RP120855). S.-M.H. is supported by grants from the NIH (P30ES006096, U01ES019480, R01ES015584, RC2ES018758 and RC2ES018789) and a VA award (I01BX000675).

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Walker, C., Ho, Sm. Developmental reprogramming of cancer susceptibility. Nat Rev Cancer 12, 479–486 (2012). https://doi.org/10.1038/nrc3220

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