Editing Nicotine (section)

===Cancer===

Contrary to [[List of common misconceptions|popular belief]], nicotine itself does not cause cancer in humans,<ref name=IARCCancerStatement>{{cite web |title=Does nicotine cause cancer? |url=https://cancer-code-europe.iarc.fr/index.php/en/ecac-12-ways/tobacco/199-nicotine-cause-cancer |website=European Code Against Cancer |publisher=World Health Organization&nbsp;– International Agency for Research on Cancer |access-date=23 January 2019}}</ref><ref>{{cite magazine | vauthors = Tolentino J |date=May 7, 2018 |title=The Promise of Vaping and the Rise of Juul |url=https://www.newyorker.com/magazine/2018/05/14/the-promise-of-vaping-and-the-rise-of-juul |access-date=June 29, 2024 |magazine=[[The New Yorker]]}}</ref> although it is unclear whether it functions as a [[tumor promoter]] {{as of|2012|lc=y}}.<ref>{{cite journal | vauthors = Cardinale A, Nastrucci C, Cesario A, Russo P | title = Nicotine: specific role in angiogenesis, proliferation and apoptosis | journal = Critical Reviews in Toxicology | volume = 42 | issue = 1 | pages = 68–89 | date = January 2012 | pmid = 22050423 | doi = 10.3109/10408444.2011.623150 | s2cid = 11372110 | type = Review }}</ref> A 2018 report by the US [[National Academies of Sciences, Engineering, and Medicine]] concludes, "{{wj}}[w]hile it is biologically plausible that nicotine can act as a tumor promoter, the existing body of evidence indicates this is unlikely to translate into increased risk of human cancer."<ref>{{cite book|title=Public Health Consequences of E-Cigarettes|chapter=Chapter 4: Nicotine| vauthors = ((National Academies of Sciences, Engineering, and Medicine, Health and Medicine Division, Board on Population Health and Public Health Practice Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems )) |veditors=Eaton DL, Kwan LY, Stratton K|isbn=978-0-309-46834-3|publisher=National Academies Press|year=2018|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK507191 | type = Review }}</ref>

Although nicotine is classified as a non-carcinogenic substance, it can still promote tumor growth and metastasis. It induces several processes that contribute to cancer progression, including [[cell cycle]] progression, [[epithelial-to-mesenchymal transition]], [[cellular migration|migration]], invasion, [[angiogenesis]], and evasion of [[apoptosis]].<ref name="Schaal_2014">{{cite journal | vauthors = Schaal C, Chellappan SP | title = Nicotine-mediated cell proliferation and tumor progression in smoking-related cancers | journal = Molecular Cancer Research | volume = 12 | issue = 1 | pages = 14–23 | date = January 2014 | pmid = 24398389 | pmc = 3915512 | doi = 10.1158/1541-7786.MCR-13-0541 | type = Review }}</ref> These effects are primarily mediated through [[nicotinic acetylcholine receptor]]s (nAChRs), particularly the [[alpha-7 nicotinic receptor|α7 subtype]], and to a lesser extent, [[β-adrenergic receptor]]s (β-ARs). Activation of these receptors triggers several [[signaling cascade]]s crucial in cancer biology, notably the [[MAPK/ERK pathway]], [[PI3K/AKT pathway]], and [[JAK-STAT signaling]].<ref name="Schaal_2014" />

Nicotine promotes lung cancer development by enhancing proliferation, angiogenesis, migration, invasion, and epithelial–mesenchymal transition (EMT) via nAChRs, which are present in lung cancer cells.<ref name=Merecz-SadowskaSitarek2020>{{cite journal | vauthors = Merecz-Sadowska A, Sitarek P, Zielinska-Blizniewska H, Malinowska K, Zajdel K, Zakonnik L, Zajdel R | title = A Summary of In Vitro and In Vivo Studies Evaluating the Impact of E-Cigarette Exposure on Living Organisms and the Environment | journal = International Journal of Molecular Sciences | volume = 21 | issue = 2 | page = 652 | date = January 2020 | pmid = 31963832 | pmc = 7013895 | doi = 10.3390/ijms21020652 | doi-access = free | type = Review }}{{CC-notice|cc=by4|url=https://www.mdpi.com/1422-0067/21/2/652/htm| author(s) = Merecz-Sadowska A, Sitarek P, Zielinska-Blizniewska H, Malinowska K, Zajdel K, Zakonnik L, Zajdel R }}</ref> Additionally, nicotine-induced EMT contributes to drug resistance in cancer cells.<ref>{{cite journal | vauthors = Kothari AN, Mi Z, Zapf M, Kuo PC | title = Novel clinical therapeutics targeting the epithelial to mesenchymal transition | journal = Clinical and Translational Medicine | volume = 3 | page = 35 | date = 2014 | pmid = 25343018 | pmc = 4198571 | doi = 10.1186/s40169-014-0035-0 | doi-access = free | type = Review }}</ref>

Nicotine in tobacco can form carcinogenic [[tobacco-specific nitrosamines]] through a [[nitrosation]] reaction. This occurs mostly in the curing and processing of tobacco. However, nicotine in the mouth and stomach can react to form [[N-Nitrosonornicotine|N-nitrosonornicotine]],<ref name=":1">{{cite journal | vauthors = Knezevich A, Muzic J, Hatsukami DK, Hecht SS, Stepanov I | title = Nornicotine nitrosation in saliva and its relation to endogenous synthesis of N'-nitrosonornicotine in humans | journal = Nicotine & Tobacco Research | volume = 15 | issue = 2 | pages = 591–5 | date = February 2013 | pmid = 22923602 | pmc = 3611998 | doi = 10.1093/ntr/nts172 | type = Primary }}</ref> a known type 1 carcinogen,<ref name=":2">{{cite web|title=List of Classifications – IARC Monographs on the Identification of Carcinogenic Hazards to Humans|url=https://monographs.iarc.fr/list-of-classifications|access-date=2020-07-22|website=monographs.iarc.fr}}</ref> suggesting that consumption of non-tobacco forms of nicotine may still play a role in carcinogenesis.<ref>{{cite journal | vauthors = Sanner T, Grimsrud TK | title = Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment - A Review | journal = Frontiers in Oncology | volume = 5 | page = 196 | date = 2015-08-31 | pmid = 26380225 | pmc = 4553893 | doi = 10.3389/fonc.2015.00196 | doi-access = free | type = Review }}</ref>