Connections of nicotine to cancer

Abstract

This Opinion article discusses emerging evidence of direct contributions of nicotine to cancer onset and growth. The list of cancers reportedly connected to nicotine is expanding and presently includes small-cell and non-small-cell lung carcinomas, as well as head and neck, gastric, pancreatic, gallbladder, liver, colon, breast, cervical, urinary bladder and kidney cancers. The mutagenic and tumour-promoting activities of nicotine may result from its ability to damage the genome, disrupt cellular metabolic processes, and facilitate growth and spreading of transformed cells. The nicotinic acetylcholine receptors (nAChRs), which are activated by nicotine, can activate several signalling pathways that can have tumorigenic effects, and these receptors might be able to be targeted for cancer therapy or prevention. There is also growing evidence that the unique genetic makeup of an individual, such as polymorphisms in genes encoding nAChR subunits, might influence the susceptibility of that individual to the pathobiological effects of nicotine. The emerging knowledge about the carcinogenic mechanisms of nicotine action should be considered during the evaluation of regulations on nicotine product manufacturing, distribution and marketing.

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Figure 1: Structure and function of nAChRs.
Figure 2: Hypothetical schemes of several carcinogenic mechanisms of nicotine action.

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Acknowledgements

The author's work on this article was supported by the grant R01ES017009 from the US National Institutes of Health, GRANT10997075 from the US Department of Defense and a research grant from the American Lung Association.

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Grando, S. Connections of nicotine to cancer. Nat Rev Cancer 14, 419–429 (2014). https://doi.org/10.1038/nrc3725

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