Nicotine and Cancer - How are They Linked?

Role of Nicotine in Cancer Causation and Progression and Spread

hand refusing to take a cigarette
What is the role of nicotine in cancer development and progression?. istockphoto.com

Does nicotine cause cancer or cause cancer to spread? What effect does nicotine have on cancer treatments? As more and more quit smoking aids containing nicotine become available, this is an increasingly important question. On one extreme lies the benefit of nicotine replacement therapy -- it can help people kick a habit known to cause cancer (and many other diseases.) On the other extreme are people who point out that nicotine can be deadly and that it was even first used as an insecticide.

Effect of Nicotine on Cancer - Different Questions and Definition of Terms

To answer this question -- the role of nicotine with regard to cancer -- the question must be broken down into several topics. As such, we should examine the role of nicotine in the following:

  • Tumor Initiation or Mutagenicity - This refers to the ability of a substance to cause the damage (mutations in DNA) necessary to convert a normal cell into a cancer cell. (This article discusses the difference between normal cells and cancer cells.)
  • Tumor Promotion/Tumor Progression - This refers to the ability of a substance to cause a tumor already present to grow more rapidly and/or spread (metastasize) to other regions of the body more rapidly.
  • Effect on Cancer Treatment - This refers to the effect a substance may have on cancer treatments, for example, if a substance inhibits or prevents the action of chemotherapy drugs. 

What Role Does Nicotine Play in Cancer?

Although studies have not been conducted on all possible effects of nicotine on all cancers.

And, many of the studies to date have been done on mice, rats, or on cancer cells grown in the lab, we do know the following:

  • Effect of Nicotine on Tumor Initiation or Mutagenicity - Recent studies have shown that nicotine has mutagenic and tumor-promoting activities. There is also evidence that nicotine can cause DNA damage - the type of damage that can lead to cancer. There is also evidence that nicotine augments the process of carcinogenesis - meaning that the process of a cell becoming cancerous in response to another substance is enhanced. This also doesn't mean it isn't dangerous for those without cancer. The effects below may occur when a cancer is present but has not yet been diagnosed.
  • Effect on Tumor Promotion and Progression - While nicotine may not be responsible for the first cells in a tumor becoming cancerous, several additional studies have shown that once a certain cancer develops, nicotine can promote the growth of the tumor. For example, nicotine has been found to promote the aggressiveness of pancreatic cancer in mice. It has also been found to promote proliferation, invasion, and migration of tumor cells in non-small cell lung cancer.
  • Effect on Responses to Cancer Treatment - Nicotine has been found to interfere with the some of the treatments for cancer, which could mean in turn that nicotine could lower the survival rates from cancer. For example, nicotine can promote resistance to the chemotherapy drug Platinol (cisplatin) in lung cancer cells.

It's important to note that, in most of these studies, nicotine is evaluated separately from tobacco smoking in order to make sure that effects are due to nicotine alone rather than other substances present in tobacco.

How Does Nicotine Work to Promote Cancer Growth and Spread and Reduce the Effectiveness of Treatment?

There are several different ways in which nicotine has been found to affect the growth and spread of a cancer.  These include:

  • Enhancing the initiation of cancer (as noted above.)
  • Stimulating tumor growth (by stimulating proteins responsible for cell division and growth.)
  • Facilitating cancer spread (for example, by improving the motility of cancer cells (as mentioned below.)
  • Enhancing angiogenesis - Nicotine may enhance the ability of cancers to produce new blood vessels needed for growth and preventing the natural death of cells that are old or abnormal (apoptosis.)
  • Causing chemoresistance - Through stimulating various pathways, nicotine may cause a tumor to be less sensitive to chemotherapy agents.

Though describing the precise mechanisms is very technical and beyond the scope of this article, a few examples of ways in which nicotine has been found to promote the growth and spread of cancers include:

  • Nicotine can work by binding with receptors called nicotinic acetylcholine receptors (nAChRs.)  In fact, this is the way in which nicotine is addictive. By activating these receptors nicotine can stimulate the growth of tumors, promote the formation of new blood vessels necessary for cancers to grow (angiogenesis) and inhibit death (apoptosis) of cancer cells. Since there are variations of the nicotinic acetylcholine receptors among different individuals, these effects may also vary among different people. (Interestingly, a stronger nicotine addiction is correlated with a higher risk of lung cancer.)
  • Nicotine stimulates a protein known as beta-arrestin-1.  This protein, in turn, enhances the mobility of certain lung cancer cells allowing them to spread and invade more easily.

Cancers Connected to Nicotine in Some Way

The effect of nicotine on initiation, progression, and response to treatment has not been studied for all cancers, but there is evidence that nicotine may play a harmful role in at least one way for the following cancers:

Further Information About Nicotine

Next Steps

If you are reading this article, you may be concerned about your own nicotine addiction, or that of a loved one. These articles give great tips on managing withdrawal from nicotine, as well as success stories from those who have found freedom from addiction.

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