Epigenetics and cancer: What the science says

Epigenetics, the study of heritable changes in gene expression without altering the DNA sequence sequence, has become a key field in understanding of cancer. From DNA methylation to histone modification and non-coding RNAs, these epigenetic changes influence tumour development and progression and offer new avenues for diagnosis and treatment. This article explores these mechanisms and their implication in various aspects of oncology, including the potential of nutrigenomics in cancer prevention.

Epigenetics in cancer diagnosis

Early and accurate detection of cancer is a major step towards successful treatment. DNA methylation, which is the process of adding methyl groups to DNA molecules, thereby modifying the activity of a DNA segment without changing the sequence itself, is a promising approach for detecting abnormal methylation patterns associated with the development of cancer. This modification can influence gene activity and is therefore crucial to understanding how certain genes can promote or prevent cancer. The detection of promoter hypermethylation has attracted a great deal of attention in cancer diagnosis.

Histone modification, which involves changes in the proteins around which DNA is wrapped, is another potential epigenetic biomarker. These proteins, known as histones, play a key role in regulating gene expression. Modifications, such as the addition or removal of chemical groups on these histones, can turn genes on or off and are therefore essential in the process of cancer development. The detection of abnormal post-translational modifications in histones is an emerging approach to cancer diagnosis and outcome prediction. In lung cancer, specific histone modifications, such as lower levels of H3 and H4 methylation, have been associated with poor prognosis and mortality.

Methylation of miRNAs is a new epigenetic biomarker in various cancers, including lung cancer. Hypermethylation of miR-124a and MiR-29 has been associated with poor prognosis in lung cancer.

Epigenetic mechanisms

Epigenetic changes can ‘switch on’ or ‘switch off’ a gene through various mechanisms, including DNA methylation, histone modification and non-coding RNAs.

DNA methylation: This involves the transfer of a methyl group to a specific position in the DNA to modulate the recruitment of proteins essential for the initiation of gene expression. In general, methylation blocks gene expression, and demethylation is necessary to remove this inhibition.
Histone modification: Histones are chromosomal proteins wrapped around DNA. Tightly wrapped histones prevent the proteins regulating gene expression from accessing the DNA, thereby inhibiting expression. Loose histone packaging has the opposite effect. Histone modification involves adding or removing chemical groups to regulate the tight or loose packing of histones.
Non-coding RNA : DNA sequences are transcribed to generate coding or non-coding RNAs. While coding RNAs produce proteins, non-coding RNAs control gene expression by various mechanisms.

Epigenetic changes in cancer

Epigenetic changes are associated with the development and progression of cancer. However, their reversible nature and somatic inheritance pattern make them potential therapeutic targets. In cancer research, epigenetics is essential for early diagnosis, detection of cancer type and the design of new therapies.

DNA methylation in cancer: Global hypomethylation of DNA is accompanied by hypermethylation in other regions. Hypomethylation induces the expression of oncogenes (cancer-promoting genes), while hypermethylation suppresses the expression of tumour suppressor genes. These collective processes initiate and promote the development of cancer.
Histone modification in cancer: Lower levels of histone post-translational modifications (methylation or acetylation) are associated with poor prognosis in prostate, lung and kidney cancer. Conversely, higher levels of a specific histone modification (H3K9ac) are associated with poorer survival in lung cancer.
MicroRNAs (miRNAs) in cancer: miRNAs are a type of non-coding RNA that bind to target messenger RNAs to inhibit their translation and subsequent protein synthesis. Changes in their structure and function can trigger disease. Some miRNAs with oncogenic function are called onco-miRNAs.

Reduced expression of miR-101 has been observed in many types of cancer, leading to increased expression of an enzyme responsible for histone methylation. This induction of methylation in tumour suppressor genes may increase the risk of cancer development.

Epigenetics in cancer treatment

Combined epigenetic therapies have shown promising results in the treatment of cancer patients, as tumorigenesis is associated with numerous epigenetic changes. It is essential toidentify the specificgenetic and epigenetic changes associated with tumorigenesis in each patient in order to make the most of these therapies.

In bladder cancer, expression of tumour suppressor genes is inhibited by the repressive polycomb complex or de novo DNA methylation. Suppression of expression mediated by the polycomb repressor complex can be treated with inhibitors of the histone methylation enzyme. Similarly, de novo DNA methylation can be blocked by DNAC inhibitorsEpigenetic therapies can be combined with conventional chemotherapy to increase treatment efficacy. A combination of chemotherapy and epigenetic drugs has been found to reduce the growth of relapsed and refractory aggressive cancers such as diffuse large B-cell lymphoma. Epigenetic drugs also help to increase the sensitivity of cancer cells to chemotherapy.

The cytotoxicity induced by high-dose chemotherapy can trigger epigenetic changes in cancer cellssuch as DNA methylation and histone acetylation. This can lead to drug resistance. Treatment with inhibitors of these epigenetic processes can suppress drug resistance and improve cancer prognosis.

Understanding the role of epigenetics in cancer is essential for developing strategies for early diagnosis, targeted treatment and improved outcomes for cancer patients. Discoveries in epigenetics are paving the way for a more precise and personalised approach to the fight against cancer. While epigenetics plays an essential role in the treatment of cancer, it is also closely linked to another important field: nutrigenomics.

What is nutrigenomics?

Nutrigenomics studies how nutrients and food compounds can induce epigenetic modifications. For example, certain foods are rich in compounds capable of influencing DNA methylation, a key process in epigenetics. Nutrients such as folic acid, B vitamins and polyphenols found in fruit and vegetables can help regulate genetic activity in a beneficial way. These compounds can activate or repress the expression of cancer-related genes, offering the potential for prevention and treatment.

In addition, regular consumption of specific foods may play a role in histone modification and the regulation of non-coding RNAs, two other important aspects of epigenetics. For example, omega-3 fatty acids, found in oily fish, are known to influence non-coding RNAs, which in turn can regulate gene expression linked to cancer development.

This interconnection between diet and epigenetics opens up fascinating prospects for cancer prevention and management, underlining the importance of a balanced, nutrient-rich diet in maintaining optimal health.

The importance of nutrigenomics in understanding cancer

Epigenetics is a complex field of biology that explores how environmental factors and human lifestyle influence gene expression. A particularly fascinating aspect of this study is nutrigenomics, which looks at how nutrition can interact with our genes and, as a result, have a significant impact on our health, including in the context of cancer.

Nutrigenomics: Diet and epigenetic modifications

Nutrigenomics focuses on how the nutrients we consume can influence our epigenetics. Our diet provides a wide range of compounds, such as vitamins, minerals and phytonutrients, which can act as epigenetic regulators.

DNA methylation: Certain nutrients, such as folic acid and vitamin B12, are essential for DNA methylation. A deficiency in these nutrients can lead to abnormalities in DNA methylation, which can contribute to the development of cancer.
Histones and diet: Dietary compounds, such as the polyphenols found in fruit and vegetables, can influence histone modification. They can help maintain a histone structure conducive to normal gene regulation.
Non-coding RNA : Certain fatty acids, such as omega-3 fatty acids, have been associated with the regulation of non-coding RNAs. These RNAs may play a crucial role in the regulation of genes involved in tumour growth.

Nutrigenomics and cancer prevention

The impact of nutrigenomics in cancer prevention is undeniable. A balanced diet rich in essential nutrients can help maintain healthy epigenetics, thereby reducing the risk of harmful epigenetic modifications linked to cancer.

For example, studies have shown that diets rich in cruciferous vegetables, such as broccoli and cauliflower, contain compounds that can support DNA methylation, helping to prevent the occurrence of epigenetic changes associated with cancer.

Source:

https://www.cureus.com/articles/76816-epigenetics-the-key-to-future-diagnostics-and-therapeutics-of-lung-cancer#!/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2802667/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008069/
https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01197-3
https://www.news-medical.net/health/Understanding-the-Vital-Role-of-Epigenetics-in-Cancer.aspx