Nicotine per se is not a substantial cause of cancer. Any cancer-related risks during short-term nicotine therapy to aid smoking cessation are insignificant compared to the risks of smoking.
Carcinogenic nicotine-derived nitrosamines have been theorized to be formed in the body under certain conditions after administration of nicotine medications, and there is some evidence for this for N'-nitrosonornicotine (NNN). The level of this carcinogen is low, and further research is needed to determine whether this level could represent a health hazard during long-term nicotine therapy. Nicotine has been shown to inhibit apoptosis (cell death) and to enhance angiogenesis in cell and experimental animal test systems. These effects could in theory promote the spread of cancers. However this risk has not been documented in people.
Carcinogenicity studies carried out in mice, rats, and hamsters demonstrate that, under normal conditions, nicotine is not carcinogenic (US Department of Health and Human Services, 2001; Surgeon General's report 2010). One study does show a low, but significant, incidence of tumors in hamsters exposed to nicotine and maintained in 60% hyperoxia, and some others suggest a possible enhancing effect of nicotine on the activity of carcinogens (US Department of Health and Human Services, 2001; Schuller et al., 1995). Other tobacco smoke constituents, such as polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, aldehydes, acrolein, 1,3-butadiene, benzene and aromatic amines, are believed to be responsible for the induction of cancers associated with tobacco use (Hoffman & Hecht, 1990; Hecht, 1999). However, two metabolites of nicotine that are formed in humans, nornicotine and 4-methylamino-1-(3-pyridyl)-1-butanone can, under certain conditions, react with endogenous nitrosating agents producing the carcinogenic tobacco-specific nitrosamines N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (Hecht et al., 2000; Carmella et al., 1997; Porubin et al., 2007). While there is no evidence for endogenous production of NNK in NRT users, some NRT users do produce NNN, sometimes in amounts greater than delivered during smoking (Stepanov et al., 2009). Further research is necessary to determine whether endogenous formation of NNN in people undergoing long-term NRT would pose a significant carcinogenic risk.
Nicotine promotes metastasis in animals with implanted tumors, speculated to be a result of enhanced angiogenesis (Heeschen et al., 2001; Cooke, 2007). Nicotine has been demonstrated to affect cellular signal transduction in several critical pathways that involve inhibition of apoptosis and stimulation of cellular proliferation (West et al., 2003; Dasgupta et al., 2006). These studies concerning inhibition of apoptosis, stimulation of angiogenesis and cellular proliferation by nicotine have been done in animals. Relevant human data are not available. The generally negative results in animal carcinogenicity tests lead to the conclusion that nicotine itself is not a significant direct, cause of cancer in people who use tobacco products, although nicotine could possibly promote cancer once initiated. Short term nicotine use for tobacco cessation is undoubtedly much safer than persistent tobacco use.
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