The Link Between Nicotine and Cancer

hand refusing to take a cigarette, but is nicotine alone harmless?

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By itself, nicotine may not play a large role in the induction (development) of cancer, but it does seem have to have an important role as a promoter—a substance that can facilitate the growth or spread of a cancer already present. That said, studies looking at e-cigarettes are again questioning whether nicotine may indeed be a carcinogen. Nicotine may also affect cancer treatments such as some chemotherapy drugs and radiation therapy, rendering them less effective. With a multitude of quit smoking aids containing nicotine available, understanding the precise roles of nicotine in cancer is critical.

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. Nicotine replacement as a method to help with smoking cessation is something that needs to be weighed against the possible risk.

Effect of Nicotine on Cancer

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: 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.
  • 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. Since metastases are the ultimate cause of death in 90 percent of people with cancer, even substances that are not associated with cancer development but do play a role in progression could be very dangerous.
  • 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.

The Role Nicotine Plays in Cancer

Although studies have not been conducted on all possible effects of nicotine on all cancers, and though many of the studies to date have been done on mice, rats, or on cancer cells grown in the lab, a significant number of studies have looked into these issues. 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.

Tumor Initiation

While nicotine has not historically been thought to play a role in the development of cancer (has not been thought to be a carcinogen), a 2018 study called that into question. In the study, nicotine exposure (via e-cigarettes) was found to lead to DNA damage—the type of damage that can lead to cancer, at least in animal models and human lung and bladder cells grown in the lab. 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.

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.

Response to Cancer Treatment

Nicotine has been found to interfere with 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.

Mechanisms Behind Nicotine and Cancer Growth

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

Stimulating Tumor Growth

Nicotine has been found to stimulate proteins involved in cell division and growth through a few different pathways.

Enhancing Angiogenesis

Angiogenesis is a term used to describe the formation of new blood vessels. In order for malignant tumors to grow beyond a few millimeters in diameter, new blood vessels must be formed to supply the tumor with oxygen and nutrients, as well as remove waste products.

Nicotine has been found to promote angiogenesis (at least in the lab) in a few different studies.

Facilitating Cancer Spread (Metastases)

One of the major ways that cancer cells differ from normal cells is that cancer cells often spread to distant regions of the body and grow (metastases). Metastases, in turn, are the cause of death in over 90 percent of people with cancer.

An increase in tumor cell migration and spread may occur in a number of different ways. According to a 2015 study, 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.

Causing Chemoresistance

Through stimulating various pathways, nicotine may cause a tumor to be less sensitive to chemotherapy agents. This has been seen with lung cancer cells exposed to platinum drugs as well as colon cancer cells exposed to 5-fluorouracil and camptothecin.

Inhibition of Cell Death (Apoptosis)

Nicotine may also inhibit the process of programmed cell death (apoptosis) of cancer cells exposed to chemotherapy or radiation therapy.

Regulation of Cancer Stem Cells

It's not known exactly why some previously treated early-stage cancers such as early stage non-small cell lung cancer can recur after lying dormant for years. One theory is that cancer stem cells are more resistant to treatments than other cancer cells. A 2018 study found that nicotine may induce the expression of an embryonic stem cell factor (Sox2) that is needed for self-renewal and maintenance of stem cell properties in lung adenocarcinoma (a type of non-small cell lung cancer). An earlier 2014 study noted similar findings with breast cancer cells, via a different mechanism.

Nicotine May Have Different Effects for Different People

One way in which nicotine may cause the effects listed above is by binding with receptors called nicotinic acetylcholine receptors (nAChRs). In fact, this is the way in which nicotine is addictive. According to a 2014 study, activating these receptors, nicotine can stimulate the growth of smoking-related cancers, promote 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.)

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:

Nicotine and Smoking Cessation

Understanding the possible effects of nicotine on cancer may be helpful for those considering methods to help with smoking cessation.

People Without Cancer

For those who do not have cancer, quit smoking aids that contain nicotine may provide greater benefits than risks. While the jury is out on whether nicotine can cause the development of cancer, we know that many chemicals in tobacco smoke can. In addition, smoking aids that contain nicotine are not recommended for people who have or at risk for heart disease.

One caveat to consider, however, is that tumors are often present for several years before they are large enough to be diagnosed. A tumor that has not yet "declared itself" as being present may still be susceptible to the cancer promoting effects of nicotine.

People Living With Cancer

For those who have cancer, quitting smoking can make a difference in a number of ways. Continued smoking can delay wound healing from surgery, and make chemotherapy, targeted therapies, and radiation therapy less effective. That said, the studies looking at the role of nicotine in cancer progression and spread suggest that alternative smoking aids that don't contain nicotine may be the better choice.

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