Does Nicotine cause Cancer?

Question

It is believed by many that Nicotine causes cancer, and passively vaping may also cause cancer due to the nicotine content.

My research into the idea whilst looking at questions such as Does 'vaping' affect your lungs? has uncovered that Nicotine is also found in various fruit and vegetables (Davis, et al. 1991; Castro & Monji, 1986; Sheen, 1988 & Domino, et al. 1993). It is also mentioned in How much nicotine is in tea and vegetables.

Further to the answers given so far by @Narusan and @wolf-revo-cats along with further research I have conducted

I feel there is more that can be gleaned regarding cancer risks of Nicotine.

Cancer Research UK says

[E]-cigarettes don’t contain cancer causing tobacco. They do contain nicotine, which is addictive, but isn’t what causes the damage from smoking.

Nicotine showed cocarcinogenic effect with DMBA (7,12-dimethylbenz[a]anthracene) in the hamster cheek pouches model (Chen & Squier, 1990), but...

To our knowledge, there are no relevant study in humans on carcinogenic effects from pure nicotine including products, such as NRT and e-cigarettes (Sanner & Grimsrud, 2015).

When looking at passive smoking and cancer, Domino et al. (1993) points out that 10g of eggplant contains the equivalent nicotine of passively smoking for 3 hours in a room with a "minimum amount" of tobacco smoke. 10g is not a lot of eggplant and passive smoking causes cancer (e.g. Hori, et al. 2016). If Nicotine causes cancer, and as eggplant, potato and tomatoes contain nicotine as well according to the studies above, would these plants cause cancer as well?

Don’t get me wrong, as an ex-smoker myself, I know how stopping boosts health. My question is whether Nicotine does cause cancer, or is it Nicotine-derived N-Nitrosamines (Hoffmann & Hecht, 1985), or is it actually Tobacco-specific nitrosamines (TSNAs) formed from tobacco alkaloids during the curing and processing of tobacco (Hecht, 1999)?

References

Castro, A., & Monji, N. (1986). Dietary nicotine and its significance in studies on tobacco smoking. Biochemical Archives, 2(2), 91-97.

Chen, Y. P., & Squier, C. A. (1990). Effect of nicotine on 7, 12-dimethylbenz [a] anthracene carcinogenesis in hamster cheek pouch. JNCI: Journal of the National Cancer Institute, 82(10), 861-864. doi: 10.1093/jnci/82.10.861 pubmed: 2110268

Davis, R. A., Stiles, M. F., & Reynolds, J. H. (1991). Dietary nicotine: a source of urinary cotinine. Food and Chemical Toxicology, 29(12), 821-827. doi: 10.1016/0278-6915(91)90109-K pubmed: 1765327

Domino, E. F., Hornbach, E., & Demana, T. (1993). The nicotine content of common vegetables. New England Journal of Medicine, 329(6), 437-437. doi: 10.1056/NEJM199308053290619

Hecht, S. S. (1999). Metabolism of Carcinogenic Tobacco Specific Nitrosamines. NIH Grant Application R01-CA081301-05 Retrieved from http://grantome.com/grant/NIH/R01-CA081301-05

Hoffmann, D., & Hecht, S. S. (1985). Nicotine-derived N-nitrosamines and tobacco-related cancer: current status and future directions. Cancer research, 45(3), 935-944. Retrieved from http://cancerres.aacrjournals.org/content/canres/45/3/935.full.pdf

Hori, M., Tanaka, H., Wakai, K., Sasazuki, S., & Katanoda, K. (2016). Secondhand smoke exposure and risk of lung cancer in Japan: a systematic review and meta-analysis of epidemiologic studies. Japanese journal of clinical oncology, 46(10), 942-951. doi: 10.1093/jjco/hyw091

Sanner, T., & Grimsrud, T. K. (2015). Nicotine: carcinogenicity and effects on response to cancer treatment–a review. Frontiers in oncology, 5, 196. doi: 10.3389/fonc.2015.00196

Sheen, S. J. (1988). Detection of nicotine in foods and plant materials. Journal of Food Science, 53(5), 1572-1573. doi: 10.1111/j.1365-2621.1988.tb09328.x

Answer 1

It is a common way to demonise substances in saying that they "cause cancer". In the case of recreational or habitual tobacco smoking there is no longer much debate over whether that is true or not. "Smoking causes cancer" is a commonly accepted fact now.

But what exactly causes cancer within this model? Smoke from a cigarette is a mixture of evaporated plant material, pyrolised material, burnt paper etc. Quite a lot of substances in differing mixtures. An exact explanation of cause and effect for each "ingredient" of smoke is much more difficult than a relatively simple epidemiological correlation and conclusion or even a lab experiment with copious amounts of smoke.

For nicotine ioslated and on itself it has recently been said that:

• In small doses, nicotine speeds up cell growth. In larger doses, it’s poisonous to cells.
• Nicotine kick-starts a process called epithelial-mesenchymal transition (EMT). EMT is one of the important steps in the path toward malignant cell growth.
• Nicotine decreases the tumor suppressor CHK2. This may allow nicotine to overcome one of the body’s natural defenses against cancer.
• Nicotine can abnormally speed up the growth of new cells. This has been shown in tumor cells in the breast, colon, and lung.
• Nicotine can lower the effectiveness of cancer treatment.

via Healthline

That can be criticised on numerous grounds. Whether a substance interferes with cancer treatments is wholly irrelevant to the question whether the substances causes it.
Assertions like these without the numbers, for example dose-response, effect sizes etc. I tend to either follow up to their sources or just ignore them altogether.

In this case the source is

Tore Sanner & Tom K. Grimsrud: "Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment – A Review", Frontiers in Oncology. 2015; 5: 196. PMID 26380225 DOI 10.3389/fonc.2015.00196

In there all of the points above quoted by healthline are present. Any yet they have to hide a caveat in the middle of the conclusion part:

At present, it is not possible to draw a conclusion whether nicotine itself may act as a complete carcinogen.

The demonisation of just nicotine seems to be mostly twofold, if we substract all the annoyances from smoking tobacco: habit or even addiction forming and limited amount of joy.

If we look just at the substance alone, and exclude smoking or vaping or liquid-preparation inhalation, what is left?

A practical outlook would be to examine nicotine replacement therapy.

Peter N. Lee & Marc W. Fariss: "A systematic review of possible serious adverse health effects of nicotine replacement therapy", Archives of Toxicology (2017) 91:1565–1594:

We conducted a systematic literature review to identify and critically evaluate studies of serious adverse health effects (SAHEs) in humans using nicotine replacement therapy (NRT) products. Serious adverse health effects refer to adverse events, leading to substantial dis- ruption of the ability to conduct normal life functions. Strength of evidence evaluations and conclusions were also determined for the identified SAHEs. We evaluated 34 epidemiological studies and clinical trials, relating NRT use to cancer, reproduction/development, CVD, stroke and/or other SAHEs in patients, and four meta-analyses on effects in healthy populations. The overall evidence suffers from many limitations, the most significant being the short-term exposure (≤12 weeks) and follow-up to NRT product use in most of the studies, the common failure to account for changes in smoking behaviour following NRT use, and the sparse information on SAHEs by type of NRT product used. The only SAHE from NRT exposure we identified was an increase in respiratory congenital abnormalities reported in one study. Limited evidence indicated a lack of effect between NRT exposure and SAHEs for CVD and various reproduction/developmental endpoints. For cancer, stroke and other SAHEs, the evidence was inadequate to demonstrate any association with NRT use. Our conclusions agree with recent statements from authoritative bodies.

Although we cannot categorically exclude the possibility that nicotine alone is a cancer causing or a cancer promoting agent with 100% certainty, we might conclude that the low level of serious adverse health effects from psychotropically effective doses in nicotine replacement therapy are a good indicator for the general safety of the miniscule levels of nicotine found in tomatoes, potatoes and even the egregious eggplant.

Conflicts of interest: This answer does not promote or advertise or justify the use of nicotine in any way. It does call for a sober evaluation of its properties. It also does promote and advertise the ingestion of vegetables disregarding the amount of nicotine in them completely.

Answer 2

There is not enough evidence either in support or in rebuttal...

EFFECTS OF CHRONIC OR REPEATED EXPOSURE:
Nicotine is a teratogen (capable of causing birth defects). Other developmental toxicity or reproductive toxicity risks are unknown. The information about nicotine as a carcinogen is inconclusive.

^cdc.gov

In summary, the findings of animal studies do not support the hypothesis that nicotine is a complete carcinogen. It is a tumor promoter in some experimental models, although not for tobacco-specific nitrosamines. Studies examining other classes of tobacco smoke carcinogens (e.g., polycyclic aromatic hydrocarbons) would need to be performed to better define the potential cancer risk inferred from animal studies.

[...]

There is insufficient data to conclude that nicotine causes or contributes to cancer in humans, but there is evidence showing possible oral, esophageal, or pancreatic cancer risks. Additionally, there is substantial experimental evidence indicating that nicotine is bioactive for a number of carcinogenic mechanisms in experimental systems. Although in vitro data are suggestive of relevant biological activity, this is not supported overall by the most recent experimental animal studies. In humans, there has been limited research and only one relatively short–term follow-up study on nicotine and cancer.

_{Surgeongeneral.gov, Chapter 5 Nicotine (PDF)}

Answer 3

I'd want to add to Narusan's answer the following: While nicotine by itself doesn't seem to be a carcinogen, to some degree it may be converted to carcinogenic N-nitrosonornicotine (a tobacco-specific nitrosamine) in the body, for example by bacterial activity. How much depends, among other things, on the route of administration.

If Nicotine causes cancer, then as Potato or Tomatoes contain Nicotine according to the studies above, they would surely cause cancer as well.

Even if that were (!) true, so what? In the probabilistic model of epidemiology “cause” is not like the ‘everyday’ conception of cause.

For example, the classification is by the strength of evidence, not the degree of risk. That's why we hear something like this:

Bacon, ham and sausages rank alongside cigarettes as a major cause of cancer, the World Health Organisation has said, placing cured and processed meats in the same category as asbestos, alcohol, arsenic and tobacco.

Therefore, I don't see a reductio ad absurdum.

On a more serious note, even with eggplants you'd have to eat 10 kg to get to the level of a single cigarette.

But that's not even why your reasoning is fallacious. It's wrong, like with the coffee cancer warnings in California, to not consider the whole product (vegetable/fruit/…). You have to balance the carcinogens vs. the antioxidants and anticancer agents.