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Gene-Environment Interaction and Cancer

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Abstract

It is widely recognized that cancer is an epigenetic disease. Hypomethylation of cytosine residues of CpG dinucleotides, site-specific CpG promoter hypermethylation, altered histone methylation and acetylation and dysregulation of miRNAs have been shown in several types of cancers. Epigenetic events are susceptible to environmental and lifestyle factors, including diet, endocrine disruptors and circadian rhythm. Nutrition is thought to be the most influential of all the external environmental factors due to its ability to affect the interplay between genome and epigenome. Nutrients affect epigenetic machinery mainly by promoting or inhibiting enzymes involved in DNA methylation and histone modifications. Therefore, poliphenols, isothiocyanates, selenium and folate, display a chemo-preventive potential. On the opposite, other nutrients, such as glucose and lipid-derived free fatty acids exert pro-tumorigenic activities. The epigenomic landscape in cancers may be modified also by environmental chemicals with endocrine disrupting activity. Plasticizers (bisphenol A and phthalates), polychlorinated biphenyls, polybrominated diethyl ethers, dioxins, pesticides (methoxychlor, chlorpyrifos, dichlorodiphenyltrichloroethane), fungicides (vinclozolin) and herbicides may have either direct (on cancer cells) or indirect (on metabolic imbalance) effects on cancer onset and progression by inducing aberrant epigenetic modifications that persist into later life, with the capacity of being transgenerationally inherited. Finally, the disruption of circadian rhythms (light, sleep/awake cycles, feeding) may also contribute to the onset and the progression of cancer-related phenotypes by impinging on epigenetic mechanisms.

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Authors and Affiliations

  1. Unità di Ricerca “Genomica del Diabete”, Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Napoli, Italy

    Vittoria D’Esposito & Pietro Formisano

  2. Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli “Federico II”, Napoli, Italy

    Maria Rosaria Ambrosio & Pietro Formisano

  3. Azienda Ospedaliera Universitaria “Federico II”, Napoli, Italy

    Giuseppe Perruolo

  4. Oncologia, Azienda Sanitaria Locale Napoli 3, Napoli, Italy

    Michele Libutti

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  1. Vittoria D’Esposito
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  1. Head of the Environmental Epigenetics Group, Institute of Experimental Genetics & German Center for Diabetes Research (DZD), Helmholtz Zentrum München GmbH – German Research Center for Environmental Health, Neuherberg, Bayern, Germany

    Raffaele Teperino

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D’Esposito, V., Ambrosio, M.R., Perruolo, G., Libutti, M., Formisano, P. (2020). Gene-Environment Interaction and Cancer. In: Teperino, R. (eds) Beyond Our Genes. Springer, Cham. https://doi.org/10.1007/978-3-030-35213-4_6

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