Epigenetics can be defined as an alteration in patterns of gene expression without any change in the nucleotide sequence of the genome.
Most of us believe that cancer is caused by errors called mutations in our genes, but interestingly, the primary reason for cancer, particularly breast cancer, is related to other factors, including the environment. There is growing scientific evidence that links environmental factors like lifestyle, food supplements, and emotional wellbeing with the onset and progression of cancer.
These factors rarely change the genetic makeup of cells, but the functional capacities of human genetics are changed through a mechanism called epigenetics.
Epigenetics can be defined as an alteration in patterns of gene expression without any change in the nucleotide sequence of the genome. It includes the study of how our environment and behavior can influence the working of our genes.
It involves reversible changes or modifications that go beyond the information that our genes encode. The proteins that interact with our DNA can determine the extent to which our genes are turned off or on through transcription.
Epigenetic modifications can be inherited from mother to daughter cells, known as mitotic inheritance, and among generations, also known as meiotic inheritance. Some of the most common ways in which epigenetics works include DNA methylation, gene silencing associated with non-coding RNA (ncRNA), histone modifications, etc.
Epigenetics and cancer
Epigenetic dysregulation can aggravate the risk of several diseases; cancer is one of them. Cancer formation is a multistep process caused by cellular abnormalities occurring as a result of genetic and epigenetic dysfunction.
Transcriptional silencing or overactivation of critical genes responsible for controlling several cell processes, including replication, repair, division, and apoptosis, can result in cancer. The literature holds numerous shreds of evidence that dictate the overexpression of oncogenes as a result of abnormal methylation patterns on their promotor sites in cancer cells.
Moreover, epigenetic silencing of DNA repair genes that reduce mutation rates and maintain genomic stability is another proof that epigenetics plays an important role in cancer through predisposition to mutations.
Methylation of DNA repair gene promoters like MGMT and MLH1 can result in A-G transitions and increased microsatellite instability. Several drugs, for example, 5-aza-deoxycytidine, a DNA methyltransferase, and many others, have been approved by the FDA to control and treat cancer. Thus, the role of epigenetics, specifically DNA methylation, in human cancers is becoming more apparent as time passes.
Food supplements and their proven significance in cancer prevention
Dietary factors and nutrition are some of the major environmental factors involved in the epidemiology of cancer through epigenetic modifications. The significance of nutrition and dietary factors in cancer prevention cannot be denied.
Recent advanced technologies and new interventions in metabolomics, genetics, and epigenetics have expanded our knowledge of the role of nutritional factors in the risk of cancer progression and prevention. Food supplements, including folic acid and several vitamins, including vitamins A, B12, B17, C, E, and beta-carotene, have been proven effective in slowing down the progression of many diseases, including cancer.
Epi-diet and cancer prevention
A new term has been proposed in cancer therapy called epi-diet, which refers to epigenetic diet. It represents a group of polyphenols, dietary bioactives, and many other secondary metabolites present in our diet or taken in the form of food supplementation that work to function as epigenetic regulators by directing epigenetic modulatory enzymes, including HDACs and methyltransferases, as well as methyltransferase inhibitors, and has shown promising results in cancer prevention and therapy.
Nutrient deficiency, particularly reduced levels of folic acid in the body, makes cells more susceptible to glucose and methylglyoxal-induced DNA damage.
Hyperglycemic Type 2 DM patients with folic acid deficiency have higher chances of developing chromosomal instability through epigenetic dysregulation. Boonma et al. conducted a study on arsenic-induced DNA damage in cells and proved that folic acid additions can prevent this nitrative and oxidative DNA damage. Another study showed that a deficiency of folate can result in cytogenic damage and is involved in the progression of colorectal cancer.
Randomised control trials have proven the efficiency of folate, zinc, and vitamin B12 supplements and their combinations in improving cellular health and reducing DNA damage by promoting genomic integrity.
Cellular oxidative DNA damage is directly linked to the levels of certain micronutrients, including selenium and vitamin A, which directly dictate their potential protective role against DNA damage and cancer progression.
Experimental studies have proved that vitamin C can counter various cellular pathways that cancer cells use for their development and progression. Similarly, vitamin C has been used pharmacologically as an enhancer of immunotherapy and a regulator of epigenetic mechanisms.
Vitamin C has also been proven to increase the production of H2O2, which has inhibitory effects on the metastasis of tumour cells. Another study stated that everyday intake of high-dose vitamin C retarded the growth of ovarian cancer and neuroblastoma as well as enhanced the activity of checkpoint kinases in experimental models, thereby reducing malignancy rates.
DNA hypomethylation was also promoted by vitamin C, which increased TET-2-dependent expression of various genes involved in DNA damage response. Vitamin C reduced tumour growth and metastasis in bladder cancer through epigenetic regulation of TET expression. Vitamin C was also proven to increase the efficacy of DZNep, a histone methylation inhibitor via EZH2, in leukaemia patients.
To conclude, micronutrients influence enzymes involved in the epigenetic regulation of various oncogenes and tumour suppressors to prevent cancer through different mechanisms, and they have also been known to reduce chemoresistance in cancer patients.
The role of food supplements in the preservation of genomic stability, the prevention of cancer, and their therapeutic abilities cannot be denied. However, scientific insights into the mechanism of action of most supplements remain limited, and they cannot replace approved therapeutic strategies against cancer.
Many dietary supplements can have adverse side effects, which may depend on the patient’s health and vary accordingly. So, it is advisable to consult your doctor before including any supplements in your diet, specifically if you are facing serious health concerns.
The article is jointly authored by Fatima Mohsin and Muhammad Mustafa.