Why “Bad Genetics” Is Not The Root Cause of Cancer, and What Is

Mutations in tumor suppressor genes and proto-oncogenes are the proximal cause of cancer, but those mutations do not happen spontaneously, nor are acquired mutations inherited due to “bad genetics”. Therefore, whatever causes those mutations is the distal and true cause of cancer.

So what causes mutations? Dr. Bruce Ame’s famous mutagenicity assay demonstrated that mutagens are everywhere in our environmment, including in many common foodstuffs. That includes the obvious ones like red meat, but it also includes unexpected ones like celery. Also included are common industrial bydproducts like BCPs. UV radiation is also mutagenic.

As Dr. Ames points out, everyone is exposed to mutagenic compounds and radiation every day, yet some people get cancers and others don’t. Therefore, mutagens per se can’t be the distal cause of cancer either. Rather, the true distal cause of cancer is what makes some people more vulnerable to mutagens than other people.

Dr. Ames favorite example of this kind of thing is micronutrient deficiencies. For instance, studies have shown that if you don’t give mice enough folate, their chromosomes undergo double-stranded breaks. Similarly, if you don’t give people enough magnesium, their bodies will ratione the magnesium and use it for essential short-term survival functions like generating ATP instead of long-term longevity functions like repairing DNA. This general pattern of rationing micronutrients is Dr. Ame’s triage theory.

Beyond micronutrient deficiencies, there are many other factors. The mold toxin ochratoxin, for instance, methylates and turns off the promoter of the Nrf2 gene. That’s a problem because Nrf2 is normally activated by oxidative stress and turns on several signalling cascades that result in the upregulation of detoxification and DNA repair pathways. A mycotoxin-methylated Nrf2 promoter therefore causes the cell to retain toxins and not repair DNA as efficiently (Fuentes 2015).

A metabolite derived from cruciferous vegetables like broccoli and brussel sprouts called diindolylmethane (DIM) has been shown to reverse the methylation of Nrf2 (Fuentes 2015). To get enough DIM to make a difference you need to take it as a supplement. Supplemental DIM is usually very expensive, but I’ve found a relatively cheap and high quality version of DIM here.

This is not an exhaustive list at all, but you get the idea. Lots of underappreciated factors make cells vulnerable to mutagens; mutagens that are not properly dealt with cause mutations; and mutations can produce a cancerous phenotype. In other words, cancer is not caused by “bad genetics”, and genetic engineering is unlikely to ever prevent or cure cancer in my opinion. Instead, we should look at what make cells vulnerable to mutagenesis in the first place.

References:

1. Fuentes F, Paredes-Gonzalez X, Kong A-NT. Dietary Glucosinolates Sulforaphane, Phenethyl Isothiocyanate, Indole-3-Carbinol/3,3′-Diindolylmethane: Antioxidative Stress/Inflammation, Nrf2, Epigenetics/Epigenomics and In Vivo Cancer Chemopreventive Efficacy. Curr Pharmacol Reports. 2015;1(3):179-196. doi:10.1007/s40495-015-0017-y.

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