discovery
Cancer is caused by accumulated damage to DNA

What causes cancer?

Cancers are becoming more common, for many reasons. The latest estimates are that over a third of adults will have a cancer diagnosis in their lifetime, some estimates even put the proportion as high as one in two adults. This increase in cancer rates is partly because we are generally living longer. The good news is that treatments are making significant improvements in cancer survival, so people are living longer with and after cancer1.

In this article we will look at some of the causes of cancer, and discuss the basics of how cancers start. For more information about some of the concepts mentioned here, see our articles on carcinogens and cancer cells.

Key points:

  • Cell function is governed by the genetic codebook, the DNA, in each cell.
  • Cancers are caused by an accumulation of errors (mutations) in the DNA, these errors change or corrupt the message that is encoded by the DNA, this causes disruption of normal cell function.
  • These errors can be caused by acquired damage to the DNA, or errors can be inherited. Environmental factors, diet and lifestyle contribute to the risks of DNA damage.
  • Many errors in DNA can be repaired by the inbuilt repair mechanisms that have evolved to keep cells healthy. However, damage to the ‘housekeeping genes’ that govern these repair mechanisms can cause the cell to become unable to repair DNA mistakes.
  • Some early cancer cells may be picked up and destroyed by the immune system, but if they persist a cancer will develop.
  • Cancers may vary in their degree of aggressiveness, as further mutations in the DNA  can cause some genes to be switched on that enable cancer spread.
  • Some cancers can be driven by hormones that target growth signals within particular tissues that are more susceptible to developing cancers because they have a high rate of cell replication.

Curve demystifies cancer so you can better understand its causes

See our video series for more info

There is no single factor that causes all cancers, but there are many factors that contribute to cancers developing. Firstly it’s important to recognize that ‘cancer’ is an umbrella term that includes many different types of cancers. There are some common features of them, but there are different factors that contribute to causing different cancer types

In this article we’ll look at factors that may cause cancers to start and contribute to them developing and progressing, some of which may be avoidable. There’s more information about dietary factors that may influence cancer risks in our articles  Cancer Fighting Foods and Cancer Diets.

Cancer starts in the DNA – the code for life

Cells carry a biological codebook, DNA, an intricate structure of paired strands. This codebook is our genetic blueprint, which defines and governs the structure and function of every cell. In this section, we’ll look at how cancer is caused by damage and dysfunction in this DNA and the processes around it.

The structure of the DNA, and the processes involving DNA, can be corrupted, causing mistakes in the messages produced. Since every function of a cell is governed by instructions coded in the DNA, this damage can cause change in the behavior of the cell and potentially cause a cancer to start. These changes that can cause cancer can be inherited, or they can be acquired.

When a cell divides, as part of renewal, repair or growth, it must first copy (replicate) the DNA and then separate the two identical sets of genes, sending one copy into each of the two daughter cells. The code within the DNA is read or ‘translated’ to govern cell processes. These processes of DNA replication and translation are carefully controlled, but they are susceptible to error, and the DNA material itself is fragile and susceptible to damage. This is how some carcinogens cause cancer. They can damage the DNA, causing mutations, and corrupt the message that the DNA carries, this can cause a cell to behave differently2-4.

Some carcinogens cause breaks or abnormal bonds in the DNA, this causes deformed arrangements in the DNA strands, so that the DNA doesn’t replicate properly, or doesn’t produce the correct message. Fortunately the body has a whole suite of repair mechanisms that can fix these mistakes in the DNA, because mistakes in DNA are surprisingly common, especially as we age.

The DNA repair mechanisms are themselves encoded by DNA, and damage to the DNA in the region of these ‘housekeeping genes’ can happen. This damage is more likely to cause a cell to become cancerous, because damage to other areas of DNA cannot be repaired effectively. When damaged DNA persists in cells it can cause a cell to become cancerous.

Inherited cancer risk

Some people inherit some particular errors or mutations in the DNA that make them more likely to develop certain cancers. For example, inheriting some mutations in the BRCA genes increase the risk of developing breast and ovarian cancer5. Many of the inherited cancers are linked to mistakes in the DNA repair genes so the cells are less able to maintain DNA integrity. In some people, the risk is related to specific tissues or organs.

However, it’s thought that more cancers are caused by acquired DNA damage6,7, and a smaller proportion of cancers are caused by inherited factors. For many people, cancers are caused by a combination of some inherited DNA errors and acquired DNA damage.

As well as damage to the DNA, structures and processes that manage and control the DNA, so- called epigenetic components, can also be changed by carcinogens and by other factors8,9. Some nutritional factors that influence cancer risk may exert their effects via epigenetic mechanisms10.  We discuss these topics in more detail in our Introductory Video Series.

Cancer is a process, not a single step11

After a cell has transformed to a cancer cell, there are many steps along the way that influence the development of cancer as a disease. Some early cancers may never be detected, as the immune system may detect them and destroy them before they become established. Early stage, low grade cancers appear to have fewer DNA mutations than more advanced aggressive cancers. These differences may be due to the tissue where the cancer starts, the genetic changes that led to the cancer starting, and the environment in the body12. As a tumour is established, genes are switched on that enable new blood vessels to be built (angiogenesis) to feed the growing tumour. Further changes in the DNA in a cancer cell can enable it to spread and cause secondary cancers (metastases), as genes that enable tissue invasion are switched on. Changes to the biological markers on the cell surface may cause the cancer cell to become less visible to the immune system.

Hormones may drive some cancers.  For example estrogen has a function of stimulating normal breast cell replication, but can also cause breast cancer cells to grow13. A number of factors may cause the breast cell to become cancerous. The high rate of cell division in breast tissue makes it more susceptible to mistakes in the DNA replication process so that abnormal cells are more likely to arise, and estrogen can target specific cell receptors that drive the growth of the cancer. Estrogen itself, and particularly some breakdown products (metabolites) of estrogen, may also directly cause mutations in the DNA in breast cells13.

Summary

To summarize, cancers are caused by errors in the DNA in cells, these errors cause corruption of the message that is encoded by the DNA. This causes disruption of normal cell function. These errors can be caused by acquired damage to the DNA, or errors can be inherited. Environmental factors, diet and lifestyle contribute to the risks of DNA damage. Many errors in DNA can be repaired by the inbuilt repair mechanisms that have evolved to keep cells healthy. However, damage can occur to the DNA in the regions of the ‘housekeeping genes’ that govern these repair mechanisms. This causes the cell to be unable to repair DNA damage. Some early cancer cells may be picked up and destroyed by the immune system, but if they persist a cancer will develop. Cancers may vary in their degree of aggressiveness, as further mutations in the DNA switch on genes that cause the cancer to spread. Some cancers can be driven by hormones that target growth signals within particular tissues that are more susceptible to developing cancers because they have a high rate of cell replication.

Cronin KA, Lake AJ, Scott S, et al. Annual Report to the Nation on the Status of Cancer, part I: National cancer statistics. Cancer. 2018;124(13):2785–2800. doi:10.1002/cncr.31551
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Murthy P, Muggia F. Women's cancers: how the discovery of BRCA genes is driving current concepts of cancer biology and therapeutics. Ecancermedicalscience. 2019;13:904. Published 2019 Feb 14. doi:10.3332/ecancer.2019.904
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Ryall JG, Cliff T, Dalton S, Sartorelli V. Metabolic Reprogramming of Stem Cell Epigenetics. Cell Stem Cell. 2015;17(6):651–662. doi:10.1016/j.stem.2015.11.012
Shukla S, Meeran SM, Katiyar SK. Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention. Cancer Lett. 2014;355(1):9–17. doi:10.1016/j.canlet.2014.09.017
D. Hanahan, D. Weinberg RA. Hallmarks of cancer: the next generation Cell, 144 (2011), 646-674
Orciani M, Caffarini M, Lazzarini R, et al. Mesenchymal Stem Cells from Cervix and Age: New Insights into CIN Regression Rate. Oxid Med Cell Longev. 2018;2018:1545784. Published 2018 Dec 2. doi:10.1155/2018/1545784
Fuhrman BJ, Schairer C, Gail MH, et al. Estrogen metabolism and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 2012;104(4):326–339. doi:10.1093/jnci/djr531

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