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Epigenetics and cancer: not so SNimPle

Epigenetics and cancer: not so SNimPle

Cancer epigenetics: are we thinking rationally?

Cancer is a devastating disease that affects millions of people worldwide each year. So, what can be done to slow its destructive path? Over the past decades billions of research dollars have been spent on trying to cure cancer in a reactive and generalist manner, attempting to halt it mid rampage through our bodies. These approaches, have proven successful in combating cancer. However, in the vast majority of cases such treatments are at the very least painful and traumatic experiences, with hugely variable success rates (from 1% at the low end to 98% at the high end). So, what about proactive treatment, are there any glimmers of hope for a future where diseases such as cancer can be halted before they even become an issue? Well… maybe.

It is easier to return back to a harbour during a storm the closer you are to the port.

We live in a world where we are much better informed about cancer than we have ever been. A world where screening programs for early detection of certain cancers are administered as standard within healthcare systems, such as the NHS. These approaches provide means by which cancer can be detected and treated earlier, increasing chances for a successful intervention. But again, with this approach we are still acting in a reactive manner, however proactively reactive it may feel. Are there any glimmers of hope for a truly proactive approach?

It is far easier to never have left the harbour during a storm than to calm the waves within one.

To understand how science is enabling a truly proactive and personalized approach to cancer, we turn ourselves to breast cancer, one of the largest cancer killers in women, and the field of genetics. Over many years, researchers have found a number of key single position genetic mutations or SNPs that are associated with an increased risk of succumbing to this horrific disease. Such mutations include those to the now infamous BRCA1 and BRCA2 genes.

What can we do with BRCA this and BRCA that?

Well, this knowledge now provides women at risk because of these mutations with a choice. With control. With an informed decision to make. To act proactively or to roll the dice. In the case of BRCA1 and breast cancer, this decision is by no means a pleasant or easy one. With the proactive treatment being a preventative mastectomy operation, but is avoiding the alternative worth it?

Nothing is ever as simple as it seems…

So, are we moving towards a future where everything is predetermined by our genes? A future where diseases may one day become choices, informed choices that we as individuals have the power to make? And can diseases such as cancer be explained by genetics alone? Well, as important as genetics is… no.

It turns out that for breast cancer incidence, and cancer incidence more generally, only a small proportion of cases can be explained by genetics. In the case of breast cancer, the proportion that can be explained by genetics alone is just 10%, and compared to most other cancers this number is quite high. For other cancer sites, such as bone, salivary gland and genital cancers, this proportion drops below a single percent.

So how does cancer develop in the first place? The quick answer to this question is that for the vast majority of cases we still don’t fully understand how cancer occurs. One of the major reasons for this being the complexity of the process itself. It’s not all doom and gloom though! Scientists are gaining exciting insights into how and why certain cancers develop that will hopefully pave the way for novel early detection methods, preventative interventions and treatments in the coming years.

What defines our actions?… our actions as a bunch of cells that is.

One aspect of cancer onset whose importance is becoming increasingly apparent is that of epigenetics. Epigenetics can be broadly defined as the study of how your DNA is organized and controlled. So why is epigenetics so important for cancer development and progression? Well, the reason is that one of the earliest stages in progression of many cancers is the misregulation of gene expression. This misregulation of gene expression results in the cells not behaving as they should. The end result being the development of cancerous cells — rebel cells that disobey the rules that govern all other cells in our bodies.

So, what do rebel cells have to do with epigenetics?

There is now increasing evidence that rebel cell formation (or cancer) is driven by changes to the epigenetics of these cells. In other words, changes to how the DNA is controlled in these cells causes changes in gene expression resulting in the formation of cancerous cells. Interestingly, the link between epigenetics and cancer is so strong that it is possible to assess cancer risk from epigenetics. For instance, recently published studies have shown that specific DNA methylation, global DNA methylation and specific histone modifications are associated with breast cancer risk. This has led to the development of epigenetic biomarkers for determining cancer risk. With some biomarkers being predictive years before diagnosis. For instance, DOK7 and BRCA1 promoter DNA methylation have both been shown to predict heightened breast cancer risk.

Epigenetic changes; what can we do?

There are many reasons why the epigenetic make up of a cell can change, and this is one of the reasons understanding the first steps of cancer onset is so complex BUT all of them can be broadly defined as being caused by changes to your environment. Your environment? Whether a free radical-induced mutation to a specific position in your DNA or alterations to your diet, anything that alters your environment has the potential to alter your epigenome. Obviously, some risk factors, such as the free radical-induced mutations, are to an extent beyond our control but there are many which are not.

Harnessing your environment.

Imagine that it were possible to know how your environment was affecting your epigenome. Imagine knowing the effect your mental health or your diet was having on your epigenome and by extension your risk of developing cancer. You would have informed choice. Proactive informed choice that would put you in control of your future. Not only that but these choices would be both far simpler to make and far less intrusive than mastectomies. This all sounds great but how close are we actually to truly proactive and personalized cancer intervention?

Is the future of proactive healthcare here?

The answer is that for certain environmental factors, the future is already here. For instance, alcohol and folate intake, two known cancer risk factors, have already been associated with changes to the epigenome. Physical exercise and a low fat diet have both been shown to reduce recurrence rates through potentially epigenetic mechanisms.

In addition, epigenetic risk factors may also be mitigated by dietary intake of classes of vegetables known to contain anti-cancerous compounds. Isothiocyanates found in broccolis and water cress are known to inhibit epigenetic proteins called HDACs in cancerous cells.

The future is bright!

In the coming years, our understanding of epigenetics and the relationship between environmental factors and cancer will undoubtedly increase. As this happens, the brief set of examples shown above will be transformed into a multitude of informative and personalized insights that will enable each of us to ensure that we are acting proactively to minimize our risks of succumbing to this tragic disease.

At Chronomics our mission is to ensure that you understand how your environment is impacting on your epigenetic information and how this pertains to your disease risks. We welcome a future where informed, proactive and personalized interventions are common place and reactive interventions can become a last resort.

Dr. Tom Stubbs is CEO and Founder of Chronomics

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