The exciting new science of epigenetics has shown that environmental factors can affect our genetic risk of cancer and other diseases. The good news is that epigenetic changes can go both ways—not only can environmental factors cause cancer; they can also prevent it and potentially cure it. Although the science of epigenetics is in its early stages, we now know that we have more control over cancer and other diseases than we thought we did. For an excellent explanation, you can watch a Nova video. Neil deGrasse Tyson explains it much better than I can, but I will summarize the basics.
Every living thing has a unique genome. A person’s genome is made of DNA and contains all the genetic instructions for that individual. The Greek prefix “epi” means “over” or “above,” and the epigenome consists of all of the chemical compounds that have been added to our genome. These compounds are not part of the DNA, but they can regulate the activity or expression of all the genes within the genome. These changes remain as cells divide, and in some cases they can be passed on from parents to children, and sometimes to grandchildren. This is the main reason that identical twins become less identical as they get older. Their DNA is still identical, but their epigenomes have diverged.
Genetic mutations have traditionally been considered to be the cause of cancer, but now we know that epigenetic changes can cause cancer as well. Many of the same things can cause both genetic and epigenetic changes, including diet, exercise, stress level, and exposure to toxins and endocrine disrupting chemicals (EDCs).
We will use an example of epigenetics that involves nutrition. The nutrients we get from food enter metabolic pathways where they are changed into molecules that can be used by the body. One of these pathways is responsible for making methyl groups. DNA methylation is the alteration that has been studied the most, and it was the first one to be linked to cancer.
Methyl is a term from organic chemistry that refers to nutrients which produce the biochemical process called methylation, in which chemicals are added to proteins, to DNA, or to other molecules, to keep your body functioning properly. Methyl-related nutrients include folate, methionine, Vitamin B12 and Vitamin B6. According to the National Cancer Institute, these nutrients have been linked to decreased risk of breast, colon and pancreatic cancer. Studies published in the American Journals of Epidemiology and the American Journal of Nutrition suggest a diet rich in these micronutrients may help you avoid cancer plus many other health problems.
Methylation, or the addition of a methyl group, is one of the processes than can modify the function of the DNA. For example, all mammals have a gene called agouti. In normal mice the agouti gene is methylated, which gives the mouse brown colored fur and a low risk of disease. However, when a mouse’s agouti gene is not methylated, it has yellow fur, is obese, and prone to diabetes and cancer. The obese yellow mice and the slim brown mice are genetically identical; the difference is caused by an epigenetic “mutation.” When the obese yellow mice were pregnant and fed a diet rich in methyl, most of their pups were slim and brown and healthy.
Animal studies have shown that a diet deficient in methyl before or just after birth causes certain regions of the genome to remain under-methylated for life. However, when adult animals are fed a diet deficient in methyl they also have a decrease in DNA methylation, but the changes are reversible when methyl is added back to the diet.
As in mice, human health is not only determined by what we eat, but also by what our mothers ate. Your mother’s diet during pregnancy and your diet as an infant can affect your epigenome in ways that remain with you as an adult. There is some evidence that fathers’ diets can also affect the epigenomes of their offspring.
The relationship between epigenetics and cancer is not well understood, but it is known that tumor cells usually have low levels of DNA methylation.
Some of the environmental agents that can interfere with DNA methylation are related to lifestyle. Among the most common lifestyle factors are smoking, alcohol consumption, UV light exposure, and factors linked to oxidative stress (excess free radicals). Oxidative stress is linked to inflammation and cancer.
Chemicals in the environment can also affect the epigenome. An example is bisphenol A (BPA), an endocrine disruptor used to make polycarbonate plastic that is used in many consumer products, including the lining of cans and plastic bottles. BPA can also reduce methylation of the agouti gene. In the lab, mice that were fed BPA were more likely to give birth to pups that were yellow and obese. However, when the mothers received methyl-rich foods along with the BPA, their pups were more likely to be slim and brown.
Epigenetic changes could play a big role in cancer prevention strategies because they occur early in the development of cancer and in some cases they might initiate it. Recently, the science of nutriepigenetics has emerged to study the influence of diet on the epigenome. One goal of nutriepigenetics is to identify chemopreventive substances which may counteract the epigenetic changes that could cause cancer. A large array of chemopreventive agents target the epigenome including:
…micronutrients (folate, retinoic acid, and selenium compounds), butyrate, polyphenols from green tea, apples, coffee, black raspberries, and other dietary sources, genistein and soy isoflavones, curcumin, resveratrol, dihydrocoumarin, nordihydroguaiaretic acid (NDGA), lycopene, anacardic acid, garcinol, constituents of Allium species and cruciferous vegetables, including indol-3-carbinol (I3C), diindolylmethane (DIM), sulforaphane, phenylethyl isothiocyanate (PEITC), phenylhexyl isothiocyanate (PHI), diallyldisulfide (DADS) and its metabolite allyl mercaptan (AM), cambinol, and …(chaetocin, polyamine analogs).
So far, most of the studies that have demonstrated epigenetic mechanisms relevant to the use of natural products to prevent cancer or promote health have involved test tubes more than animals and humans. We hope that one day a nutritionist will be able to look at your epigenome and prescribe foods and supplements that will prevent or cure cancer.
Jean-Paul Issa, M.D., former co-director of The University of Texas MD Anderson Cancer Center’s Center for Cancer Epigenetics, has said,
The idea of epigenetic therapy is to stay away from killing the cell. Rather, what we are trying to do is diplomacy, to change the instructions of the cancer cells. You see, cancer cells start out as normal cells. They have the set of instructions that is present in every one of our cells. In the process of becoming cancer, a lot of these instructions are forgotten because specific genes that regulate the behavior of a cell are turned off by epigenetics. And epigenetic therapy really aims at reminding the cell that, “Hey, you’re a human cell, you shouldn’t be behaving this way.” And we try to do that by reactivating genes, by bringing back the expression of these genes that have been silenced in the cancer cell and letting those genes do the work for us.
Since they are not aiming to kill the cancer cells, treatments can be more gentle and easier for patients to tolerate than chemotherapy.
Epigenetics has become a hot topic, and the pharmaceutical companies are working to develop epigenetic drugs. A few have already been approved by the FDA for the treatment of some types of cancer, especially leukemia. While they still need a lot of work to figure out efficacy, side effects, dosages, etc., it is hoped that they will eventually be able to prevent and/or reverse different kinds of cancer.Several epigenetic modulators are now being investigated specifically for treatment of breast cancer.