Unhealthy genes are a contributing factor in cancer development. Oncogenes refer to genes that cause cancer, while tumor suppressor genes work to stop the disease. When regular genes start malfunctioning, the result can be cancer. You already know that genes serve as the body’s instructions. They instruct a cell on its future form and function. If things weren’t running well, we couldn’t do our jobs. A mechanism is in place to prevent harmful genes from being expressed and keep beneficial ones active. Epigenetics refers to this type of modification.
Modifications to the genome called epigenetic alterations are passed down from one generation to the next without altering the DNA sequence. The DNA sequence is constant from cell to cell, but epigenetic tagging and packaging regulate gene expression. DNA methylation, histone variations, post-translational modifications, nucleosome positioning factors, and the formation of chromatin loops and domains are all examples of how this process controls chromatin structure.
How could this possibly cause cancer? Cancer (carcinogenesis) can occur, for example, if a tumor suppressor gene is inappropriately silenced or an oncogene is activated. Methylation, a chemical alteration of DNA, is a critical component. To begin, let’s clarify the procedure by defining it.
The four bases that makeup DNA are adenine, guanine, cytosine, and thymidine, but methylation cytosine counts as a fifth. When a cytosine comes before guanine (CpG), DNA methyl-transferase (DNMT) adds a methyl group to the cytosine. CpG areas are not symmetrical but are found in clusters called CpG islands in the promoter regions. The beginning of a gene contains the promoter, which is responsible for initiating transcription. The gene will never be expressed if the champion is turned off.
Cancers with methylation abnormalities have been recognized for 20 years. Hypo-methylated regions activate ordinarily inactive genes, such as those that have been added by viruses or are part of the X chromosome. Tumor suppressor genes are silenced in hypermethylated regions.
We know that foods can aid cancer prevention because we understand the aberrant methylation in malignancies. Does diet affect epigenetics in any way? Yes!
Nutrigenomics refers to investigating food components and their influence on disease through epigenetics. This is a rapidly expanding area of study. If you type “nutrigenomics” into Google, you will get 127,000 results.
Based on epidemiological research, it appears that some foods are better than others. DO NOT EAT RED MEAT, processed meat, grilled meat, dairy products, animal fat, or partially hydrogenated fats. Omega-3 fatty acids, whole grains, and foods high in fish, fruits, and vegetables are all good choices.
Whether terrible or healthy, foods have epigenetic impacts that can be studied; in this article, I will discuss the epigenetic effects of some foods shown to reduce the risk of developing cancer.
Green tea, cruciferous vegetables, and grapes are all foods that can alter your genes in this way. Antioxidants in food are typically the subject of discussion. Polyphenols, included in many healthy foods, can also affect genes and are just as significant as antioxidants. Flavonoids, one type of polyphenol found in many fruits and vegetables, have received the most attention for their purported health advantages. Tea has flavanols and various flavonoids; cruciferous vegetables include isothiocyanate; grapes and berries have anthocyanidins; citrus fruits and flavanone; onions contain flavonols; soy contains isoflavones (genistein).
While all tea contains some polyphenols, green and white tea contain significantly more. There is evidence that drinking green tea can help prevent cancer. Drinkers of green tea in China have a 50% lower risk of developing stomach or esophageal cancer (Carcin 2002; 23 (9): 1497), and oral leukoplakia can be treated by drinking two cups of green tea per day in combination with a topical tea extract (J. Nutri Biochem 2001; 12 (7): 404).
Green tea not only has strong antioxidant properties, but it also aids in maintaining proper DNA methylation. Tumor suppressor genes can be activated again after chemically silencing by methylation, as shown in research on esophageal cancer cells (Cancer Research 2003;63:7563) using EGCG from green tea.
Epidemiological studies have shown that cruciferous vegetables, including broccoli, cauliflower, kale, and Bok choi, can reduce the risk of developing cancer. These potent vegetables stimulate DNA methylation, which prevents tumor suppressor genes from being silenced and also triggers enzymes that degrade carcinogens. Cruciferous vegetables help reduce the carcinogenic effects of cigarette smoke by blocking the production of nitrosamine-DNA adducts and inhibiting aberrant methylation.
Resveratrol, found in grapes, is beneficial to heart health and has anti-cancer properties. Grapes stop cancer from starting or spreading by blocking angiogenesis. They function instead through modulating histones rather than through any methylating processes like those described above.
The DNA strand (chromatin) is primarily made up of histones, which are proteins. Using them as spools, DNA can be compressed to a size 30,000 times less than if left unwrapped. How the genes are wound influences which are accessible and available to be turned on or off; therefore, this process not only permits the long DNA chain to fit into a cell but also plays a role in gene expression. If the spool were rolled the opposite way, various genes would be exposed, and their face would be altered.
After translation, modifications like acetylation, methylation, phosphorylation, and ubiquitination are made to histones. Except for the phosphorylation of serine or threonine, all alterations occur at lysine residues. By altering the charge of the histone, acetylation causes the protein to relax its hold on the DNA strand, allowing it to unwind and expose the genes for transcription or repair.
Gene transcription occurs when histone tails (H3, H4) are acetylated, while gene silencing occurs when histone tails are deacetylated. The purpose of histone deacetylases is to keep deacetylated sites that way.
Grapes contain resveratrol, which stimulates Sirtuins, specifically SirT1 (Sir2 proteins). Histone deacetylation, Sir2-like proteins can be found in at least seven organisms. Famine conditions trigger animals’ sirtuin production. They appear to have a protective influence on one’s health. Starvation increases an animal’s lifespan. Rodents lived 50% longer and showed fewer signs of chronic disease when their caloric intake was cut by 40%. Rodents get the same health benefits when fed a diet containing resveratrol.
Deacetylation of histones by resveratrol leads to chromatin tightening and decreased DNA transcription. Life extension, improved cardiovascular health, and cancer prevention may all result from this DNA silencing. This is why eating grapes or drinking red wine is good for you. How many glasses of red wine per week is ideal? No one knows, but the alcohol content in more than two glasses daily may nullify any positive effects. Until further information is available, I wouldn’t recommend consuming more than this. Although the results are encouraging, more study is required.
Although the human genome project has dramatically increased our understanding of disease in the genomic era, a focus on genetics alone is insufficient. Understanding how genes are turned on or off requires the complex notion of epigenetics. More research into the causes of disease and the development of potential therapies to silence harmful genes while activating protective ones are both attainable goals. Moreover, these studies will show that dietary changes can alter gene expression, reducing the risk of developing or curing cancer. The study of the effects of nutritional molecules (nutrients) on genes is called nutrigenomics, and it has the potential to revolutionize our approach to nutrition. Green tea, cruciferous vegetables, and grapes are all excellent choices, but those are only a few of the healthiest meals. When it comes to your health, eating more fruits and vegetables is always a good idea.
St. Louis is home to oncologist Dr. Robert Avery. He is interested in nutritional strategies for cancer prevention and conventional cancer treatment. He runs Citrine Sun, an organization that sells information and natural vitamins to cancer patients throughout their treatment. His website, [http://www.citrinesun.com], features a newsletter with helpful information and details on supplements that might improve your health. Email Dr. Avery at AskDrAvery@citrinesun.com with any questions you may have.