When it comes to cancer, early detection greatly increases the chance of successful treatment. This is because early stage cancer often has not yet had the chance to metastasize (spread) to other parts of the body.
Early detection is particularly significant in the outcomes of cancers of the1:
While some cancers have screening methods that assist in their early detection, for example breast cancer can be screened for using Mammograms, other types of cancer are far more challenging to detect in the early stages. This has left medical scientists faced with the challenge of finding a way to identify a one-in-a billion cancer-specific mutation present in the blood of an early stage sufferer.
The types of 'liquid biopsies' currently in use are limited in terms of early stage cancer detection because they examine samples for tumour DNA, which during the early stages of cancer, is not always present in the blood in large enough amounts to be detected.
Now, a scientific team at the Princess Margaret Cancer Centre led by Dr Daniel De Carvalho, a qualified immunologist with postdoctoral training in cancer epigenomics, has combined liquid biopsies with epigenetic alterations (i.e. changes in the way genes are expressed) and machine learning that has proven to detect and classify early stage cancers.
How does this new testing work?
When you saw the words 'epigenetic alterations', you may have wondered what exactly that means and the explanation that followed (changes in the way genes are expressed) may not have helped much either. If you don't have a medical background, in order to properly understand this, you'll need a crash course in basic biochemistry and genetics…
What is epigenetics?
Put simply, epigenetics is the study of biological mechanisms that can either turn genes on or off.
To better understand this, you need to know the following about genetics:
- The body is made up of cells, every instruction they need to work efficiently and perform their various functions is contained within a chemical known as DNA (deoxyribonucleic acid).
- DNA is made up of an estimated 3 billion nucleotide bases (organic molecules that form the 'building blocks' of DNA), these occur in 4 basic types: adenine, cytosine, guanine, and thymine2.
- The order (or sequence) that these bases occur in within our bodies can be thought of as the 'instructions' for life and are known as genes. Within the nucleotide bases the are an estimated 20 to 25 thousand genes that give the body instructions on how to make vital proteins that trigger the various biological actions required for life-giving functions.
Epigenetics essentially influences how genes (remember to think of them as 'instructions' or 'signals') are interpreted by cells and how the proteins they produce are made. A gene regulatory protein carries all of this information and attaches to a specific sequence of letters in the DNA.
Here are a few other things that you need to know:
- Genes are controlled by epigenetics. Certain things in life can cause specific genes to be turned on (i.e. activated) or off (i.e. deactivated) by the gene regulatory protein which also recruits enzymes that add or remove epigenetic tags that ultimately enable cells to 'remember' what they are supposed to be doing long-term3.
- Each of us are unique thanks to epigenetics. Different combinations of genes being activated or deactivated is what makes us who we are, but it can also lead to illness.
- Epigenetics is in everything. All aspects of life from what you eat to when you sleep, and even how you exercise and spend time with causes chemical changes around genes that can eventually turn them on or off. In addition, some disease, like cancer, can turn genes away from their normal, healthy state, this is referred to as an 'epigenetic alteration'.
- Epigenetics is reversible. While epigenetics changes can be inherited and accumulate over a person's lifetime, researchers have found that they can manipulate the enzymes that either add or remove epigenetic tags from a gene and restore its normal, healthy function4.
What the findings published in the International Journal of Science, Nature5, describe is not only a way to detect the type of cancer present, but also identify it earlier than ever before, even before symptoms appear.
In order to do this, the team looked at epigenetic alterations (which are tissue and cancer-type specific) instead of DNA mutations. This allowed for the identification of thousands of unique cancer types. Big data was then applied using machine learning (AI) to classify and identify the presence of cancerous DNA in blood samples in order to match them with the type of cancer present.
A comparison of 300 patient's tumour samples sourced from seven disease sites and samples obtained from disease-free donors, as well as an analysis of cell-free DNA in the blood, were used to do this. Findings showed that the DNA in the blood of every sample matched the tumour DNA.
The research has already been expanded, profiling and matching over 700 tumour and blood specimens for additional types of cancer in a laboratory setting.
Going forward, the team will analyse data from existing larger population studies where participants blood has been collected months or even years prior to a cancer diagnosis being made. Thereafter, their new method will need to be validated by prospective studies for cancer screening.
This ultimately means that this specific early detection cancer blood test may only be available in future. Nevertheless, it is a promising study for those involved in cancer research to build on and for the rest of us to follow.
In the meantime, remember that early detection could save your life, so don't miss you regular screenings and check-ups, and if you notice anything unusual, err on the side of caution and see your doctor to have it checked out.
1. World Health Organisation. Early detection of cancer. Available: https://www.who.int/cancer/detection/en/ [Accessed 15.11.2018]
2. U.S. National Library of Medicine. 13 November 2018. What is DNA? Available: https://ghr.nlm.nih.gov/primer/basics/dna [Accessed 15.11.2018]
3. The University of Utah: Genetic Science Learning Centre. The Epigenome Learns From Its Experiences. Available: https://learn.genetics.utah.edu/content/epigenetics/memory/ [Accessed 15.11.2018]
4. International Journal of Science: Nature. June 2013. Epigenetics: Reversal tags. Available: https://www.nature.com/articles/498S10a [Accessed 15.11.2018]
5. International Journal of Science: Nature. November 2018. Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Available: https://www.nature.com/articles/s41586-018-0703-0 [Accessed 15.11.2018]