The thermodynamics of epistasis vs cancer

November 27, 2013 | James Kohl

In “Moving forward,” which was the next to the last section of my 2013 review, I wrote (with my emphasis):

“Evidence from genome-wide analysis suggests that polymorphisms cause alterations in neural connections and signaling in olfactory pathways, which contribute to natural variation in olfactory perception in flies (Swarup et al., 2013). That evidence links olfactory/pheromonal input to genetically predisposed species-specific behavior via previously unmodeled epistatic interactions that must occur throughout the lifecycle transitions of all organisms. Thus, the epigenetic ‘tweaking’ of the immense gene networks that occurs via exposure to nutrient chemicals and pheromones can now be modeled in the context of the microRNA/messenger RNA balance, receptor-mediated intracellular signaling, and the stochastic gene expression required for nutrient-dependent pheromone-controlled adaptive evolution. The role of the microRNA/messenger RNA balance (Breen, Kemena, Vlasov, Notredame, & Kondrashov, 2012; Duvarci, Nader, & LeDoux, 2008; Griggs et al., 2013; Monahan & Lomvardas, 2012) in adaptive evolution will certainly be discussed in published works that will follow.

The microRNA/messenger RNA balance has since been used to model to identify an epigenetically-effected thermodynamically-modulated signature of health and disease associated protein folding that includes the aberrant protein foldings of cancer. The thermodynamics of epistasis are compared in the context of aberrant foldings, which are typically linked to mutation-initated changes. See for details: miRNA and mRNA cancer signatures determined by analysis of expression levels in large cohorts of patients.

Most researchers seem to still be thinking in terms of mutations that perturb the thermodynamics of protein folding. Here, they admit they do not know what enables epistasis, which they refer to as a balance state. Instead, they use the balance state common to different cancer types as a “robust thermodynamic reference.”  Therefore, it is important to note that “…modifying even a single biomolecule connection in the cancer-specific gene network reverses the cancer state phenotype, reducing cancer cell proliferation and altering cancer cell physiology in vitro and on a single-cell level.”

That fact is the clearest indicator that I have seen of what is required for a typically maintained epistasis devoid of perturbations and aberrant protein folding.  The typical balance state of epistasis is not likely to be due to mutations. In my model, epistasis is constrained by nutrient uptake and the pheromone-controlled physiology of reproduction. That explains why cancers are not inherited but people may have a genetic predisposition for certain cancer types due to transgenerational epigenetic inheritance and the post-natal epigenetic effects that may modify a single biomolecule in the cancer-specific network.

Characterization of  breast, lung, ovarian, and prostate carcinoma patients in the context of perturbed epistasis may therefore lead to characterization of epistasis that is nutrient-dependent and pheromone-controlled via the physics of the thermodynamically-modulated chemistry of the conserved molecular mechanisms that enable adaptations sans mutations. This will happen as researchers more closely examine epistasis not associated with modifications of single biomolecules associated with diseases, but those associated with adaptive evolution in species from microbes to man that is nutrient-dependent and pheromone-controlled.

Unfortunately, there is no money to be made by discovering readily available nutrients for use in cancer treatment, or for prevention due to prescribed diets and common sense.



James Vaughn Kohl

James Vaughn Kohl

James Vaughn Kohl was the first to accurately conceptualize human pheromones, and began presenting his findings to the scientific community in 1992. He continues to present to, and publish for, diverse scientific and lay audiences, while constantly monitoring the scientific presses for new information that is relevant to the development of his initial and ongoing conceptualization of human pheromones.