Genes and epigenetics and cancerThe cause or causes of cancer have been debated for hundreds of years. Now, because there is technology to look at the gene, the focus has become the gene. Many markers, genetic amplifications, point mutations, etc. have been found that supposedly delineate hard-coded genotypic changes that lead to cancer for specific organs and tissues. And the list continues to grow. However, many of these so-called mutations may be found in healthy cells. The question then becomes whether genetic changes are the real molecular cause of cancer? Research over the past few years suggests that they are not.

Epigenetic modifications are potentially reversible changes in gene function that occur without a change in DNA sequence (genotype). In other words, epigenetic changes come from how the gene is expressed not the hard-wiring of the genetic sequence or code itself. And some of these epigenetic modifications are now being identified with carcinogenesis. According to researchers at the University of California at San Francisco, “DNA methylation and histone modifications are important epigenetic mechanisms of gene regulation and play essential roles both independently and cooperatively in tumor initiation and progression.” For example, the hypermethylation of some regulatory regions (i.e. CpG islands) can inactivate some tumor suppressor genes (i.e. BRCA1, hMLH1, p16INK4a, APC, VHL).

The critical role that epigenetic changes play in cancer etiology has been identified through a number of subtle experiments. One in particular is worth mentioning. A study at a major Children’s Hospital using a mouse model transferred the cell nucleus from a medulloblastoma cell (a type of aggressive brain cancer mainly found in children) to a normal cell. Incredibly, the nucleus from the cancer cell nucleus did not turn the normal cell into a cancer cell. One of the researchers concluded that the study, “Shows that so-called epigenetic factors are key elements in the development and maintenance of tumors.”

So why is this important? It’s important because evidence suggests that the epigenome can be influenced by the environment which means that epigenetic modifications that lead to carcinogenesis may be reversible by changing the environment. (Does this help explain observations regarding pleomorphic theory – that bacteria actually become modified as the environment changes?) This also implies that orthodox and experimental therapies have failed because they are missing the big picture. For example, chemo and radiation both try to destroy every single transformed cell with cytotoxic therapies. Beyond the statistical improbability of this approach, how rational is it when the biological and cellular environment has created and is probably continuing to create epigenetic changes leading to cancer in the first place. (Does this explain why patients with hematological cancers relapse after allogeneic stem cell or bone marrow transplantation?)

Even gene therapy which is a reasoned theory may actually be a misinformed therapy because it aims to insert genes into an individual’s cells. Assuming that you could supplement a defective mutant allele with a functional one, how does that help when the problem may reside outside the genetic code? Instead, if epigenetics are as important to cancer as they seem to be, the goal should be to change the environmental conditions that led to the epigenetic modifications in the first place.

So what effects epigenetics? We know that toxins and carcinogens induce important epigenetic alterations that can lead to cancer. Can the removal of toxins and carcinogens reverse the unhealthy epigenetic state? If it can it will provide a biochemical and genetic basis for what alternative practitioners have been saying for years – that detoxification followed by the creation of a healthy milieu with appropriate diet and supplements benefits cancer patients. Unfortunately, that simple question may go unanswered for some time because most researchers in this area are taking the predictable approach based on reductionism. They believe they can manipulate this subtle and complex system (i.e. changing our epigenome) by focusing on singular mechanistic aspects. (This approach is often driven by the pharmaceutical industry which needs to patent specific molecules in order to control their market price.) While basic bench science is needed to understand the pathways, a more valuable approach to changing the epigenome may actually come from nutrition.

For example, when scientists at Duke University changed the diet of agouti mice (large fat mice that are susceptible to cancer and diabetes) their offspring were slender and brown and did not display the parent’s susceptibility to these chronic diseases. One of the researchers was quoted as saying, “It was a little eerie and a little scary to see how something as subtle as a nutritional change in the pregnant mother could have such a dramatic impact on the gene expression of the baby.” And in November 2003 researchers at Rutgers found that green tea could prevent cancer in animals through epigenetic pathways.

So the question remains – can diet (perhaps one rich in methyl donors like onions, garlic, beets) change one’s epigenome and if so can it change the epigenome of a cancer cell so it becomes a healthy cell?

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