Epigenetic instability and cancer vs nutrient-dependent stability
May 2, 2014 | James Kohl
Excerpt (with my emphasis): “DNA methylation at epigenetically variable CpGs in normal tissue and enhanced cancer progression suggests that epigenetic instability may both precede and accelerate the evolution of cancer. ”
Reported as: 30-year puzzle in breast cancer solved
Excerpt (with my emphasis): “Collectively, these findings indicate that CTCF is major tumor suppressor gene in human cancer and highlights the power of the mouse models to prove that a candidate gene has a function in cancer. These results have implications for understanding the origin of DNA methylation alterations in cancer and suggest that epigenetic instability may both precede and accelerate the emergence of cancer.”
“This answers a 30 year riddle in cancer research”, said Dr. Kemp. “And it shows once again, as we first showed in 1998, that one hit is enough“.
My comment: The power of the mouse models to epigenetically link DNA methylation and instability to cancer may lead others to examine nutrient-dependent DNA methylation and healthy genomic stability. If so, they might realize that there is no such thing an the evolution of cancer or the evolution of species. In the mouse to human model of a nutrient-dependent change in a base pair, DNA methylation, and amino acid substitution linked to genomic stability manifested in changes in teeth, hair, sweat, and mammary tissue (see Kohl, 2013 for review) it is clear that ecological variation led to ecological adaptation in a population of modern humans. It is also clear that the ecological adaption is controlled by the metabolism of food to species-specific pheromones which control the physiology of reproduction. Therefore, it may be important for more people to start thinking in terms of nutrient-dependent DNA methylation and ecological adaptation instead of in terms of mutations and the evolution of cancer or the evolution of species.
Because genomic stability is clearly due to one-carbon metabolism, base pair changes, DNA methylation, and amino acid substitutions that differentiate the cell types of individuals in all species, the genomic stability of all species is obviously nutrient-dependent and pheromone-controlled. This means that species do not arise from mutations and natural selection that somehow lead to evolution. It also means that cancers do not evolve. Cancers arise due to errors in protein folding that lead to genomic instability in cancerous cells. However, as these authors have shown via the mouse model of human breast cancer, atypical DNA methylation may lead to mutations.
Two questions arise:
1) What causes the mutations in breast cancer?
2) Why are the mutations not found in healthy (ecologically adapted) mammary tissue?
There are now many articles that link obesity to increased cancer risk. If cancers do not evolve, but are like healthy ecologically-adapted tissues, excess caloric intake probably perturbs one-carbon metabolism and causes base pair changes that lead to atypical DNA methylation, which destabilizes the healthy genome. Given what is currently known about transgenerational epigenetic inheritance, it should be clear why breast cancer — and sometimes other cancers — tend to run in families. In those families, dietary management to avoid obesity and disease might be more beneficial than anything else a woman could do to avoid breast cancer.