BBC News: Is oestrogen involved in oral cancer?

“Oestrogen 'may fuel oral cancer' in young women,” reported BBC News. It said that head and neck cancer has become more common in younger women over the past decade, but is still most common in men between the ages of 50 and 74.

The US laboratory research behind this story found that treating pre-cancerous tongue cells with oestrogen increased production of an enzyme called CYP1B1. The CYP1B1 enzyme appears to make pre-cancerous cells move and divide, which may make the cells more likely to become cancerous. This effect was not seen in cells that were already cancerous.

Studies such as this are important as they give scientists an idea about what triggers the development of cancers. However, it is very early research and more studies will be needed before we know whether head and neck cancers could be prevented or treated with drugs targeting oestrogen or the CYP1B1 enzyme.

Smoking and excessive alcohol consumption remain the most important and established risk factors for head and neck cancers.

Where did the story come from?

The study was carried out by researchers from the Fox Chase Cancer Center in Pennsylvania. Funding was provided by the National Cancer Institute and the Commonwealth of Pennsylvania. The study was published in the peer-reviewedjournal Cancer Prevention Research.

The BBC provided balanced coverage of this story, noting the early nature of the research.

What kind of research was this?

This laboratory research looked at the effect of oestrogen on the development of a type of cancer called squamous cell carcinoma of the head and neck (HNSCC). This cancer mainly affects the mouth, nasal cavity, pharynx (throat) and larynx (voice box).

The researchers say that HNSCC is the sixth most common type of cancer in the US. Alcohol and smoking are major risk factors for this cancer, but many people develop it without being exposed them. A recent study suggested that most of these cases were in women, leading the researchers to suggest that female hormones could be responsible, although head and neck cancers are more common in men than in women.

This type of laboratory study is a good first step to test the likelihood of a theory. However, even if such a theory were shown to be plausible, further evidence from animal and human studies would be needed to confirm the findings.

What did the research involve?

The study mainly involved human cells grown in the laboratory from early- and late-stage head and neck cancerous growths (lesions) from men and women. To ensure that the cells used were as similar as possible, the cells were taken from oral HNSCC affecting the tongue.

The researchers tested whether these cells contained the proteins for making, binding and breaking down oestrogen, and the two related genes CYP1B1 and CYP1A1. They also assessed whether these proteins were present in cancerous, pre-cancerous or normal tissue taken from various head and neck sites in 128 patients affected by HNSCC.

They then looked at what happened if HNSCC and normal cells were treated with oestrogen. The researchers also examined what happened if they switched off the CYP1B1 gene, in particular whether it affected cell movement, division or death.

What were the basic results?

The researchers found that proteins involved in binding and breaking down oestrogen were present in pre-cancerous and cancerous HNSCC cells grown in the laboratory. These proteins were also present in tissue from both males and females, and levels of a protein that binds to oestrogen (called oestrogen receptor beta) and the CYP1B1 enzyme (the product of the CYP1B1 gene) were higher in HNSCC tissue than normal tissue.

Treating pre-cancerous HNSCC cells with oestrogen in the laboratory caused the CYP1B1 gene to increase in activity about threefold. However, when cancerous HNSCC cells were treated with oestrogen, an increase in CYP1B1 gene activity was not seen. Treating pre-cancerous HNSCC cells with oestrogen did not affect their movement or division. When the researchers switched off the CYP1B1 gene in these cells, however, they became less able to move and divide.

Exposing pre-cancerous HNSCC cells to oestrogen also reduced the number of cells that died by “cell suicide” (apoptosis). Treating these pre-cancerous cells with the anti-oestrogen drug fulvestrant blocked the effect of oestrogen and restored apoptosis to normal levels.

How did the researchers interpret the results?

The researchers concluded that their findings provide a new insight into how head and neck cancers develop. They say that CYP1B1 could be a new target for drugs that could prevent cancers developing from pre-cancerous head and neck lesions.

Conclusion

This early research suggests that oestrogen and CYP1B1 may have a role in the development of head and neck cancers from pre-cancerous lesions.

Only precancerous cells derived from one patient were used in these experiments. Ideally, they should be repeated in cells derived from other patients to confirm the results. Also, as this study mainly looked at cells from cancers of the tongue, cells from other HNSCC sites, such as the nasal cavity and throat, will need to be examined to see whether oestrogen has similar effects on cells from all sites.

Beyond this, much further research will need to take place before we know whether any head and neck cancers could be prevented or treated by drugs targeting oestrogen or CYP1B1.

Importantly, smoking and excessive alcohol consumption remain the most important and established risk factors for head and neck cancer. These types of cancers are more commonly seen in men than in women.