How do telomeres affect cancer?

How do telomeres affect cancer?

Telomeres shorten as we age and the risk of cancer increases as we get older; here we explore some ways telomeres affect cancer risk.

Cancer is a leading cause of death worldwide and with rates of many cancers increasing year on year, it is a priority research area in terms of improving understanding, diagnosis and treatment.

The area of cancer research that we are particularly interested in focuses on better understanding the links between telomeres, telomerase and cancer.

Telomeres and cancer

Telomere length can be considered one of the biological mechanisms for controlling the healthy functioning and lifespan of cells.

In some cases, this biological mechanism can go wrong, meaning cells begin dividing uncontrollably i.e. tumor growth occurs. This is called tumorigenesis, or the formation of cancer.

Telomere length decreases with each cell division, and therefore over time, as we age, our telomeres shorten. Read about this in more detail here.

Normally, when telomeres reach a critically short level, cell division is halted, this is called replicative senescence. This can prevent unrestricted growth of damaged cells.

The decrease of telomere length can therefore be considered as a tumor suppressor mechanism.

It may seem paradoxical, but it has been discovered that short telomeres are often found in cancer cells. This can, in some cases, be as a result of defective telomere maintenance.

Although short telomeres are a barrier to continued cell proliferation, when other genetic mutations occur, this can be overridden (in a process called crisis), allowing cell division to continue.

Associations between very long telomeres and increased risk of certain cancers, for example melanoma, have also been found and can be associated with genomic instability.

In these instances, cell division is not halted by critically short telomeres triggering a response. Therefore, cells continue to proliferate and a tumor can grow.

Having balanced telomere length, between normal parameters for age (i.e. not too long or too short), is associated with optimal function.

Telomerase and cancer

In order to continue to proliferate with the presence of short telomeres, the potential tumor cells need to overcome this barrier.

One way in which this can be achieved is for the cells to express the enzyme telomerase.

Telomerase acts to synthesize the DNA repeats that can maintain and extend telomere length.

Normally only active at very low levels in somatic cells (if at all), increased activity of telomerase is a known hallmark of cancer. Telomerase is found to be active in 85–95% of cancers. Learn more about telomerase here.

Expression of the telomerase gene (TERT) can be up-regulated in tumors via multiple genetic and epigenetic mechanisms. Mutations in the TERT gene promoter region, driving higher expression, are among the most common genetic abnormalities in cancer cells.

Cancer tests and treatments

A number of approaches are being investigated that involve inhibition of telomerase as a cancer treatment, although there have been hurdles with these.

Testing cells for telomerase activation, or the cancer-specific expression of TERT, is an avenue being investigated as a potential biomarker for a cancer test. However, there have also been obstacles with this.

It is known that individuals with telomere biology disorders (TBDs), and very short telomeres, have a significantly increased risk of specific cancers. These include acute myeloid leukemia and solid tumors such as head and neck squamous cell carcinomas.

Studies have examined the use of telomere length as a risk factor biomarker for small cell lung cancer and as a prognostic biomarker for both chronic lymphocytic leukaemia and multiple myeloma.

There are many factors that play a role in the development of cancer, with cancer types being different diseases, and this is a complex field still under investigation. Research is ongoing in this important area.

RepeatDx is actively involved in many different areas of research. Read more here.

If you would like to get in touch to discuss a prospective research collaboration, please use our contact form.

Sources
Alter, B, P., Giri, N., Savage, S, A., Rosenberg, P, S. Cancer in dyskeratosis congenita. Blood. Vol: 113, 26, 2009, p.6549-6557. https://doi.org/10.1182/blood-2008-12-192880.
Hyatt, S., Jones, R.E., Heppel, N.H., et al. (2017), Telomere length is a critical determinant for survival in multiple myeloma. Br J Haematol, 178: 94-98. https://doi.org/10.1111/bjh.14643
Jang, J.S. et al. Telomere length and the risk of lung cancer. Cancer Science. 2008; 99: 1385-1389. https://doi.org/10.1111/j.1349-7006.2008.00831.x.
Lin, T.T., Norris, K., Heppel, N.H., et al. (2014), Telomere dysfunction accurately predicts clinical outcome in chronic lymphocytic leukaemia, even in patients with early stage disease. Br J Haematol, 167: 214-223. https://doi.org/10.1111/bjh.13023
Okamoto, Keiji, and Hiroyuki Seimiya. Revisiting Telomere Shortening in Cancer. Cells. vol. 8,2 107. 31 Jan. 2019, doi:10.3390/cells8020107.
Shay J,W and Roninson I, B. Hallmarks of senescence in carcinogenesis and cancer therapy. Oncogene. 2004 Apr 12;23(16):2919-33. doi: 10.1038/sj.onc.1207518. PMID: 15077154.
Stanley, S. E., & Armanios, M. (2015). The short and long telomere syndromes: paired paradigms for molecular medicine. Current Opinion in Genetics & Development. 33, 1–9. doi:10.1016/j.gde.2015.06.004.
Stewart, S, A. and Weinberg, R, A. Telomeres: Cancer to Human Aging. Annual Review of Cell and Developmental Biology. 2006 22:1, 531-557. https://doi.org/10.1146/annurev.cellbio.22.010305.104518.
Trybek, T., Kowalik, A., Góźdź, S., & Kowalska, A. (2020). Telomeres and telomerase in oncogenesis (Review). Oncology Letters. 20, 1015-1027. https://doi.org/10.3892/ol.2020.11659
World Health Organization. Fact Sheets: Cancer. Available at: https://www.who.int/news-room/fact-sheets/detail/cancer. Last Accessed 23 June 2021.
Yuan, J.-M. et al. Leukocyte telomere length in relation to risk of lung adenocarcinoma incidence: Findings from the Singapore Chinese Health Study. Int. J. Cancer. 2018; 142: 2234-2243. https://doi.org/10.1002/ijc.31251.