DHEA and cancer prevention

TP53 and DHEA

This note was inspired by a very well-written, easy-to-read, but very long and complicated dissertation on the anticancer function of DHEA, entitled “DETECTION OF A NOVEL, PRIMATE-SPECIFIC ‘KILL SWITCH’ TUMOR SUPPRESSION MECHANISM THAT MAY FUNDAMENTALLY CONTROL CANCER RISK IN HUMANS: AN UNEXPECTED TWIST IN THE BASIC BIOLOGY OF TP53″,
by Jonathan W Nyce, In: Endocr Relat Cancer. 2018 Nov; 25(11): R497–R517., Published online 2018 Jun 25. doi: 10.1530/ERC-18-0241, PMCID: PMC6106910, PMID: 29941676 , at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106910/   

DNA DAMAGE AND MALIGNANT TRANSFORMATION

Our cells are constantly exposed to a variety of cellular stressors and are prone to DNA damage, which can lead to mutation, formation of abnormal genes and eventually, cancer.
Therefore, to protect cells from malignant transformation, the cells’ nuclei carry a special gene called TP53.

TP53 activates other genes, “KILLER GENES”, which can arrest cell metabolism and kill the cell.
This is a natural process called apoptosis, which is good because cells with cancerous potential are destroyed.
However the cells only carry tiny quantities of TP53 and it exists in a dormant, inactive form.

When DNA is damaged, TP53 is induced to accumulate in the cell nucleus and is converted into an active form, which triggers the killer genes to induce cell cycle arrest and/or apoptosis, depending on how much DNA damage has occurred.

If the damage is mild, cell metabolic slowdown permits DNA repair, but if the situation is bad enough, TP53 triggers the killer genes to destroy the cell.
In this way dangerously damaged cells are prevented from cloning themselves and producing daughter cells with damaged DNA and cancer potential.
This idea is supported by the fact that TP53-deficient mice develop spontaneous cancers.

MUTATON OF THE TP53 GENE, ITSELF.

The background point is that TP53 blockade by mutant TP53 depends on an enzyme, glucose-6-phosphate dehydrogenase (G6PD):
G6PD facilitates production of NADP and
NADP inactivates any normal TP53, keeping the abnormal cell alive.

NOW, THE CRUX OF THE MATTER:

(1) Many years ago (BACK IN THE ’80S), DHEA, the “mother hormone” made by our adrenal glands and our brains, was observed, in mice, to inhibit spontaneous breast cancer and chemically induced tumors of the lung and colon.
In mice it also stopped tumour formation by a carcinogen named DMBA and another called TPA.
In fact it was proved to be effective in stopping cancer formation generally, excepting that it promoted liver cancer in rats. This action of DHEA remained a mystery for decades, but recently (2018) there has been a breakthrough: now we know that DHEA potently blocks G6PD, thereby stopping NADP formation.
Without NADP, there is nothing to stop TP53 from working and it is free to trigger killer genes.
Therefore effectively, DHEA has the potential to discourage new cancer initiation.
(Of course, DHEA may not be effective against all cancers and as yet there have been no human trials, so what we are talking about here is a potential use in prevention of cancer, not about curing someone with an existing tumour).

(2) Many of us fail to produce normal amounts of DHEA ab initio, perhaps as a consequence of PTSD suffered in childhood, so when we all begin to lose 1% of DHEA production at age 26, high DHEA producers start from normal and low producers, from whatever they had in their teens.
Thus by age 80, the highest DHEA producers at age 25 are down to 10-20% of their original level and poor producers at 25 are down to zero.

(3) I have no certifiable answers, but I do have a lot of obvious questions, like
Do we make cancers because we don’t make enough DHEA?
If I take DHEA as a supplement, will it prevent cancer?
If I have a cancer, will DHEA stop it?
Why don’t all doctors know about this ? …… Well actually, I myself only just found it, 3 years after publishing !

REFERENCES

(1) Role of p53 in Cell Death and Human Cancers: Toshinori Ozaki1 and Akira Nakagawara , Cancers (Basel). 2011 Mar; 3(1): 994–1013.Published online 2011 Mar 3. doi: 10.3390/cancers3010994, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756401/

(2) Detection of a novel, primate-specific ‘kill switch’ tumor suppression mechanism that may fundamentally control cancer risk in humans: an unexpected twist in the basic biology of TP53, Jonathan W Nyce,
2018 Nov;25(11):R497-R517., oi: 10.1530/ERC-18-0241. Epub 2018 Jun 25.
PMID: 29941676, PMCID: PMC6106910, DOI: 10.1530/ERC-18-0241, https://pubmed.ncbi.nlm.nih.gov/29941676/

Published by Dr. Gervais Harry

I am a Toronto-trained Urologist. I practiced in downtown Toronto, from 1977 to 1997, when I went to Saudi Arabia as chief of Urology at the Armed Forces (teaching) hospital in Tabuk. Returning to Toronto in Y2000, I switched to family practice. In 2007, began to prescribe Hormone Restoration Therapy and in 2012, I became a member of the American Academy of Antiaging Medicine [A4M]. I successfully wrote the A4M's written examination in December, 2013 and In May, 2016 I passed the oral examination, for accreditation as a BHRT consultant. In 2014 I began BHRT practice in Collingwood, Ontario and in January, 2017, joined the Stone Tree Naturopathic Clinic. Now I am 82 and have retired, but it seems wasteful to jettison my learning and experience: the medical establishment knows nothing of BHRT / Functonal medicine and I feel obliged to offer my knowledge in the interest of those who are willing to think outside the box. MY QUALIFICATIONS: MB, BS, (from UWI), 1964. LMCC 1969. FRCSC (Urology), 1974. ECFMG 1984. Florida license 1998 [inactive], ABAARM Certification [A4M], 2016. I am a Member of CSAMM [the Canadian Society for Aging and Metabolic Medicine], the OMA&CMA, SUSO, CUA, RCP&S/C. PRACTICE TO DATE: Consultation in Functional Medicine, including assessment of Chronic Fatigue Syndrome, Fibromyalgia, Andropause, Menopause, Teenage and Postpartum Depression/Panic Attacks, Thyroid Hormone malfunction, Infertility, Sexual Dysfunction and “the Undiagnosable”. ALL ARE WELCOME to read, comment or question!

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