N.B. This science review was originally published in Optimyz Magazine in January 2012 by Mandy Wintink, PhD.
Epigenetics & Cancer
We have all likely been touched by cancer either directly or indirectly. The most prominent time for me was when my grandmother was diagnosed with colon cancer 13 years ago. It forced me to evaluate the role my diet could have on the development of cancer inside of me.
Although the exact causes of cancer are unknown, it is clear that cancer cells have an abnormal capacity to divide uncontrollably and form tumors. More recently, epigenetic changes are becoming important pieces of the cancer puzzle. Epigenetics are giving us insight into how cancer is triggered and progresses and how we can intervene in the development of cancer.
Epigenetics, as mentioned last issue, is the study of heritable changes that lie outside of the DNA sequence. Whereas genetics involves the code of the DNA, and for example, whether a gene is present or not or whether a gene has undergone a mutation, epigenetics primarily involve 1) the silencing and activation of genes through altered DNA methylation patterns, 2) histone modifications, and 3) chromatic remodeling - all of which alter gene expression. Genetics are relatively stable, but epigenetics provide a mechanism for how the environment (including diet) can have an effect the expression of a person’s genes.
DNA methylation is the best known epigenetic marker. It’s the footprint the environment leaves on the DNA. It is also well known for its role in many forms of cancers. For example, hypermethylation in specific DNA regions silences genes that suppress tumor growth (known as tumor suppressor genes), which leads to tumors (and cancer). Alternatively, hypomethylation activates specific genes that are known for their potential to be cancerous. These genes are known as ‘oncogenes’ and their activation also leads to cancer.
Diet can affects DNA methylation and can affect some types of cancer, like colorectal cancer (CRC). There are recent estimates that diet can prevent up to 80% of CRC. The relationship between CRC and diet was first recognized when scientists noticed that CRC was much higher in Westernized societies, where people consumed high-calorie diets and were less physically active. It was then discovered that there are specific parts of a diet that both promotes and prevents cancer. For example, red and processed meat, substantial consumption of alcoholic drinks, body fat and abdominal fatness are believed causes of CRC, as is food containing animal fats or sugar. On the other hand, foods containing dietary fibre, garlic, milk, calcium, folate, vitamin D, and selenium,
as well as non-starchy vegetables, fruits, and fish seem to protect against CRC.
The dietary effects on cancer seem to happen two ways: directly, by affecting the gut lining, and indirectly, when the blood content of specific nutrients and hormones shift the body homeostasis in a negative way, resulting in genetic and epigenetic changes, including the silencing of tumor suppressor genes.
Altered DNA methylation in many cancers, not just CRC, show promise as a biomarker for cancer susceptibility. This is important because some of the methylation changes occur prenatally and in childhood long before cancer develops. By having a marker, lifestyle changes could be adopted to reduce future incidences of cancer manifesting. This concept coincides with Dr. Alfred Knudson’s 25-year old 2-hit theory of cancer, which is currently a popular way of understanding that it is not just one factor ultimately causes cancer.
Alterations in DNA methylation is also reversible, even through diet, and potentially under some of our control. This exciting area of epigenetics and diet have paved the way to a new field now called ‘nutrigenetics’. Needless to say, epigenetics serves as a promising areas of cancer research in everything from causes to biomarkers to therapeutic intervention. If this interests you further, I would suggest checking out http://www.dietandcancerreport.org/.