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Review
, 9 (1), 63-9

Review: The Contribution of Both Nature and Nurture to Carcinogenesis and Progression in Solid Tumours

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Review

Review: The Contribution of Both Nature and Nurture to Carcinogenesis and Progression in Solid Tumours

Iain Joseph Hyndman. Cancer Microenviron.

Abstract

Cancer is a leading cause of mortality worldwide. Cancer arises due to a series of somatic mutations that accumulate within the nucleus of a cell which enable the cell to proliferate in an unregulated manner. These mutations arise as a result of both endogenous and exogenous factors. Genes that are commonly mutated in cancer cells are involved in cell cycle regulation, growth and proliferation. It is known that both nature and nurture play important roles in cancer development through complex gene-environment interactions; however, the exact mechanism of these interactions in carcinogenesis is presently unclear. Key environmental factors that play a role in carcinogenesis include smoking, UV light and oncoviruses. Angiogenesis, inflammation and altered cell metabolism are important factors in carcinogenesis and are influenced by both genetic and environmental factors. Although the exact mechanism of nature-nurture interactions in solid tumour formation are not yet fully understood, it is evident that neither nature nor nurture can be considered in isolation. By understanding more about gene-environment interactions, it is possible that cancer mortality could be reduced.

Keywords: Cancer; Carcinogenesis; Gene-environment; Mutations; Oncogenes; Tumour suppressor genes.

Figures

Fig. 1
Fig. 1
Factors contributing to the acquisition of the hallmarks of cancer in a solid tumour cell. This schematic shows only some of the critical and complex interactions involved in carcinogenesis. Mutations in genes coding for key regulators of cell cycle, growth and proliferation (green stars) arise due to insult from both exogenous and endogenous sources. These mutations (genetic instability) are likely to work synergistically to produce a solid tumour. Tumour promoting inflammation plays a key part in tumour development and has a role in sustaining proliferation and in activating invasion and metastasis. STAT3, NF-κB and AP-1 are transcription factors found within tumour-associated macrophages (TAMs), the tumour microenvironment and the tumour cell itself which lead to the activation of IL-8 and VEGF. IL-8 and VEGF are also activated by hypoxia and play key roles in inducing angiogenesis. (Me) = gene promoter methylation which can result in silencing of TSGs. (GF) = growth factor binding to its receptor and activating the MAPK pathway, resulting in cell proliferation. ROS = reactive oxygen species, shown here to be produced by mitochondria in the cytoplasm as part of normal cellular metabolism. (Deregulation of cellular energetics [Dereg. Cell Energetics] is also depicted, whereby the tumour cell switches from aerobic respiration in the mitochondria to anaerobic glycolysis within the cell cytoplasm. This metabolic alteration is thought to play a role in carcinogenesis)
Fig. 2
Fig. 2
Environmental factors involved in the development of some cancers. There are many environmental factors that play a role in the development of cancer. As well as directly damaging DNA (green stars), environmental factors work synergistically with each other to cause mutations. Some of these interactions are shown above; however, this figure is not complete: these interactions are infinite and are potentially bi-directional. Not all of the exposures shown above are needed for cancer development. (Me) = gene promoter methylation which can result in silencing of TSGs

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