What is Epigenetics?

There are many different biological processes that are essential for development and growth, and often, tumor growth can occur when these same processes go awry. For instance, it has been well researched that much of embryogenesis — the developmental stages of an embryo after the egg is fertilized by a sperm — is governed by changes in gene expression. When gene expression is altered or not performed correctly by the body, it can lead to uncontrolled cell growth and eventually tumor formation.

By studying the changes in gene expression, referred to as epigenetics, we can better understand when and how tumors develop, and in turn utilize these changes as detection, diagnostic and prognostic markers for colorectal cancer.

Originating from Greek “epi” which means “above or beyond”, epigenetics refers to the study of heritable changes in gene expression. Unlike genetics which is concerned with the genome, genes and how these are inherited, epigenetics focuses on the factors that affect how genes work. Simply put, epigenetics studies the ‘switches’ that turn genes on and off, though controlling gene expression is not nearly so binary or straightforward.

Epigenetic modifications are the ways in which gene expression is controlled, and these modifications involve changes to the structure of DNA or the proteins that bind to it, which can affect how genes are transcribed and translated into proteins. These changes can be passed down through generations, and can affect an organism's traits and risk for diseases.

DNA methylation

One of the most well-known epigenetic modifications is DNA methylation, which involves the addition of a methyl group to a cytosine base in DNA. This modification typically represses gene expression by preventing the binding of transcription factors and other proteins to the DNA. DNA methylation patterns can be passed down through cell division and in some cases, across generations, making them a potential mechanism for the transmission of environmental influences on gene expression.

Histone modification

Another common epigenetic modification is histone modification. Histones are proteins that help package DNA into chromatin, which affects how easily genes can be accessed and transcribed.

Histones can be modified in a number of ways, including acetylation, methylation, phosphorylation, and ubiquitination, which can either promote or repress gene expression depending on the specific modification and location on the histone. Research so far has found that invasive colorectal cancer correlates with higher levels of histone methylation, though the exact causal relationship remains to be determined.

Epigenetic modifications can be influenced by a variety of factors, including environmental exposures such as diet, stress, and toxins.

For instance, folate or vitamin B9 maintains genomic stability by regulating DNA biosynthesis, repair and methylation. However, alcohol consumption, one of the known risk factors of colorectal cancer, decreases folate absorption and increases its excretion. This depletion of folate and interference with its metabolic pathway can induce gene-specific DNA hypermethylation and global DNA hypomethylation. Through different multi-step pathways, the depletion of folate as a result of external influences such as alcohol can thus lead to carcinogenesis.

The study of epigenetics has important implications for our understanding of gene-environment interactions, as well as for the development of new treatments for diseases. For example, epigenetic therapies are being developed that target specific epigenetic modifications, such as DNA methylation or histone acetylation, in order to alter gene expression and treat diseases such as cancer.

In addition, epigenetics is also shedding new light on the role of nature versus nurture in shaping an individual's traits and risk for diseases. While genetics plays a significant role in determining an individual's risk for certain diseases, epigenetic modifications can be influenced by a variety of environmental factors and can potentially be modified through interventions such as diet, exercise, and drug therapies.

Epigenetics is an emerging field of study growing in importance as it sheds new light on the complex interplay between genes and the environment. By understanding the mechanisms underlying epigenetic modifications and their role in health and disease, researchers are gaining new insights into the factors that influence gene expression and developing new strategies for the prevention and treatment of diseases.