One of the causes of cancer is abnormal genes. The genes that cause cancer are called oncogenes and the genes that prevent cancer are called tumor suppressor genes. Cancers can occur when normal genes do not work normally. Genes, as you know, are the blueprints of the body. They tell a cell what it will be and what it will do. We could not function if the process does not run well. There is a system designed to keep the good genes working and suppress the bad genes. This process is called epigenetics.
Epigenetic changes are modifications of the genome that are heritable during cell division, but do not involve a change in the DNA sequence. Gene expression is not regulated by DNA sequence, which is the same in all cells, but by epigenetic labeling and packaging. This process regulates chromatin structure through DNA methylation, histone variants, post-translational modifications, nucleosome positioning factors, or chromatin domain and loop organization.
How can this cause cancer? Well, if a tumor suppressor gene is abnormally turned off or an oncogene is turned on, then cancer (carcinogenesis) can occur. One key is a chemical change in DNA called methylation. First, we need to define the process to make it clearer.
DNA contains four bases: adenine, guanine, cytosine, thymidine, but there is a methylated fifth base cytosine. DNA methyl transferase (DNMT) produces methyl cytosine where cytosines precede guanine (CpG). The CpG areas are not symmetrical but rather grouped into CpG islands located in promoter regions. The promoter region is the region at the beginning of a gene and controls the initiation of transcription of the gene. If the promoter is off, the gene is never expressed.
Abnormal methylation in cancer has been known for 20 years. Hypomethylated areas activate normally silent areas, such as genes inserted by viruses or inactive genes linked to the X chromosome. Hypermethylated areas silence tumor suppressor genes.
We know that cancers have abnormal levels of methylation and we know that food can help prevent cancers. Is there a link between food and epigenetics? Yes!
The study of nutrients in food and their effect on disease through epigenetics is known as nutrigenomics. This is a growing field, in fact, it is exploding. A Google search for the term nutrigenomics produces 127,000 entries.
Epidemiological studies suggest that there are good and bad foods. BAD: red meats, processed meats, grilled meats, dairy, animal fats, partially hydrogenated fats. Good: fish, fruits, vegetables, nuts, omega-3 fatty acids, whole grains.
You can study the epigenetic effects of good or bad foods. I’m going to talk about some of the foods that prevent cancer and how their mechanisms include epigenetic effects.
Foods with epigenetic effects include green tea, cruciferous vegetables, and grapes. We usually hear about antioxidants and foods. Antioxidants are important, but there are beneficial substances in food called polyphenols that can affect genes. Of the polyphenols, there are different forms, but flavonoids are the most cited for their health benefits and are found in a variety of vegetables and fruits. Types of flavonoids include flavonoids in tea, isothiocyanate in cruciferous vegetables, anthocyanidins in grapes and berries, flavonone in citrus fruits, flavanols in onions, isoflavones (genistein) in soybeans.
All tea contains polyphenols, but the highest levels are found in green and white teas. Green tea has been well studied and appears to have anticancer benefits. In China, green tea drinkers are 50% less likely to develop gastric or esophageal cancer (Carcin 2002; 23 (9): 1497), and 2 cups daily added to topical tea extract reversed oral leukoplakia (J Nutri Biochem 2001; 12 (7): 404).
Green tea has powerful antioxidant effects, but it also helps balance normal DNA methylation. In fact, a study in esophageal cancer cells showed that EGCG in green tea can activate tumor suppressor genes that had been chemically silenced by methylation (Cancer Research 2003; 63: 7563).
Cruciferous vegetables include broccoli, cauliflower, kale, Bok choi, and their anticancer effects have been shown in epidemiological studies. These powerful vegetables not only induce enzymes that break down carcinogens, but also inhibit DNA methylation, allowing tumor suppressor genes to thrive. Inhibiting abnormal methylation also helps cruciferous vegetables inhibit the action of cancer-causing tobacco smoke by preventing the formation of nitrosamine-DNA adducts.
Grapes, which contain reserveratrol, are great for heart health and have anticancer activity. Grapes work by preventing the formation or initiation and promotion of cancers. They do not have methylation actions as discussed above, but they work by modulating histones.
Histones are the main protein component of the DNA chain (chromatin). They act as spools for the DNA to roll up, which then shortens the length of the DNA to 30,000 times shorter than an unwrapped strand. This process not only allows the long strand of DNA to fit into a cell, it also plays a role in gene expression because the way genes are wound affects which ones are exposed and available to turn on or off. Spinning the reel in a different way would expose other genes and change their expression.
Histones are modified after translation by acetylation, methylation, phosphorylation, ubiquitination. Changes occur in lysine residues (except for phosphorylation of serine or threonine). When histone is acetylated, the charge changes and the histone loosens its grip on the DNA strand and the DNA unwinds, exposing genes to be transcribed or repaired.
When histone tails (H3, H4) are acetylated, genes are transcribed, when deacetylated genes are turned off. Histone deacetylases act to maintain deacetylated sites.
Resveratrol, found in grapes, activates Sirtuins; SirT1 (Sir2 proteins). There are at least 7 Sir2-like proteins and they are histone deacetylators. Sirtuins are induced in animals during states of starvation. They seem to have a life-preserving effect. Interestingly, when an animal starves, it can live longer. When rodents’ calorie intake was reduced by 40% in rodents, they actually lived 50% longer and appear to have fewer chronic diseases. The same benefit occurs when rodents receive resveratrol in their diet.
Resveratrol deacetylates histones causing tighter packing of chromatin and a lower level of DNA transcription. This silencing of DNA is believed to be the life-prolonging mechanism, heart health, and its beneficial actions in preventing cancer. That is why grapes or red wine are beneficial for health. How much red wine should you drink? No one knows for sure, but any beneficial effects could be nullified after two glasses a day due to alcohol. I would not recommend drinking more than this until more is known. The data is very promising, but more research is needed.
Our knowledge of the disease expanded in the genomic era due to the human genome project, but studying genes is not enough. Epigenetics is a very important and complicated concept that helps explain how genes are turned on or off. As more studies are completed, we will be able to unlock disease mechanisms and produce new therapies that could turn off bad genes and turn on good genes. More importantly, these studies will show how food affects your genes and can prevent or reverse disease or cancer. Nutrigenomics, the study of how chemicals in food (nutrients) affect genes, is a growing field and promises to change the way we look at and eat our meals. Some of the more beneficial foods include green tea, cruciferous vegetables, and grapes, but don’t stop there. The more fruits and vegetables, the better your health.