Behind the Headlines

Friday April 24 2009

The study did not specifically look at nicotine gum

The cancer risk from using nicotine gum and lozenges is higher than previously thought, The Times has reported. According to the newspaper new research has found that the nicotine levels “that are typically found in smoking cessation products” can interact with a mutation that increases the risk of cancer.

This study has looked at normal and cancerous mouth tissue and cells in the laboratory, examining the level of activity of the FOXM1 gene, which is active in many tumours, Researchers then looked at the effects nicotine had on these cells and the activity of the gene.

While nicotine increased cancer-like properties of some cells in the laboratory, these findings do not prove that nicotine replacement products are specifically associated with an increased risk of cancer. What is already clear is that smoking increases risk of cancer and quitting will reduce people’s risk. Nicotine replacement products can be an important source of help for some people trying to quit, and therefore help them reduce their cancer risk. People using these products should follow the advice available from their GP, pharmacist or nurse and included on product information leaflets.

Where did the story come from?

This research was conducted by Emilios Gemenetzdis and colleagues from Queen Mary University of London, and other cancer research centres in the UK and Malaysia. The study was funded by the Medical Research Council and the Institute of Dentistry, Barts and the London School of Medicine and Dentistry and Queen Mary University of London. The study was published in the peer-reviewed scientific journal, PLoS One.

What kind of scientific study was this?

This was a laboratory study looking at the activity of a gene called FOXM1 in tissues and cells from head and neck cancers plus normal tissue, and how chemicals that could potentially cause cancer affect the gene’s activity.

The FOXM1 gene is known to be highly active in many human tumours, but it is still unclear exactly what action and role it plays in the development and progression of cancer.

The researchers obtained a number of cell and tissue types for examination from 75 patients. These were:

  • normal tissue from the human mouth lining,
  • normal mouth lining cells,
  • tissue from head and neck cancers (head and neck squamous cell carcinomas, which include mouth cancers), and
  • abnormal (precancerous) tissue from the mouth.

The researchers looked at whether the FOXM1 gene is switched on in these cells and tissues, and how active it was. They also took thin slices of these tissues, or cultures, of the cells grown in the laboratory and used antibodies to the FOXM1 protein (which is made by the FOXM1 gene) to determine whether the protein was present, and if so, how much was present.

Use of tobacco and betel (a plant whose leaves are chewed in some Asian countries) are risk factors for developing head and neck cancer. The researchers thought that chemical compounds in these substances called alkaloids, including nicotine and two other alkaloids from betel, could be increasing the activity of the FOXM1 gene.

To test this theory the scientists used various cell types grown in the laboratory: premalignant mouth cancer cells, malignant mouth cancer cells and malignant tongue cancer cells. They exposed these cells to levels of nicotine that might be expected in the mouths of people chewing tobacco and looked at the effects on FOXM1 activity and cell survival. They did the same with the two alkaloids from betel.

The scientists then took premalignant mouth cells and genetically engineered them so that the FOXM1 gene was overactive. They took some of these cells and some control cells with normal FOXM1 activity and looked at the effect of adding nicotine to them. In particular, they were looking at whether these cells would be able to form –‘colonies’ – clumps of cells that could grow without being attached to the petri dish. This is a characteristic of malignant cells. They also carried out various other experiments to look at the characteristics of these cells.

What were the results of the study?

The FOXM1 gene was not very active in normal mouth tissue, more active in precancerous mouth tissue and most active in tissue from head and neck cancers. The FOXM1 protein was also present at low levels in normal mouth tissue, at higher levels in precancerous mouth tissue and at the highest levels in tissue from head and neck cancers.

Adding nicotine to premalignant mouth cancer cells, malignant mouth cancer cells and tongue cancer cells in the laboratory increased the activity of the FOXM1 gene. The two chemicals that they tested from betel did not have this effect. At high levels of nicotine, some of the premalignant mouth cells died but the cancerous mouth and tongue cells did not.

The researchers also found that if the premalignant mouth cancer cells were genetically engineered to have an overactive form of the FOXM1 gene and then treated with nicotine they could form colonies of cells that could grow without being attached to the petri dish.  This property is a characteristic of cells that are malignants. This did not happen if the cells only had the overactive form of the FOXM1 gene, or were just exposed to nicotine.

What interpretations did the researchers draw from these results?

The researchers concluded that their findings suggest the FOXM1 gene plays a role in the early development of head and neck cancer. They add analysis of FOXM1 activity could potentially be used as a diagnostic marker for early detection of this type of cancer.

What does the NHS Knowledge Service make of this study?

This study has looked at the activity of the FOXM1 gene in normal and cancerous mouth tissue and cells in the laboratory, plus the effects of nicotine on this activity and the behaviour of these cells.
On their own, these findings do not indicate whether the use of nicotine replacement products is associated with an increased risk of mouth cancer. This would require studies specifically comparing the rate of these cancers in users and non-users of these products.

What is already clear is that smoking is associated with an increased risk of cancer, including mouth cancer. Quitting smoking will reduce people’s cancer risk, and the use of nicotine replacement products will help some people to achieve this, and therefore help reduce their cancer risk.

People using these products should follow advice from their healthcare professionals (GPs, pharmacists or nurses) and consult product information leaflets for guidance on how long these nicotine replacement products should be used for.

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Edited by NHS Choices