DNA Methylation, DHEA, and Cancer
Copyright 2015, James Michael Howard, Fayetteville, Arkansas, U.S.A.
I suggest DNA methylation is an evolutionary consequence of reduced levels of dehydroepiandrosterone (DHEA) and is involved in cancer initiation.
It is my hypothesis that low DHEA is involved in cancer initiation. (In 1994, I first suggested that low DHEA is directly involved in initiation of oncogenes: “An Explanation of Cancer and the Increase in Cancer: High Testosterone, Low DHEA and Breast Cancer,” at: http://anthropogeny.com/An%20Explanation%20of%20Cancer%20and%20the%20Increase%20in%20Cancer.htm which appeared first in publication: Annals of Internal Medicine 2005; 142: 471-472 .)
It is also my hypothesis that DNA methylation is part of the mechanism of evolutionary selection of DHEA. I think DNA methylation occurs / increases when DHEA is low. (“Dehydroepiandrosterone, Sleep, and DNA Methylation,” at: http://www.anthropogeny.com/DNAmation.html ) For sake of example, DHEA is low during sleep, therefore, I suggest this is why DNA methylation increases during sleep. DNA methylation is common in cancer.
Therefore, I suggest low DHEA is the cause of high DNA methylation which is characteristic of cancer initiation. However, once cancer is initiated, cancer absorbs DHEA for growth at the expense of the host. This increased, rapid growth caused by increased DHEA results in reduced DNA methylation. Low DHEA (increased DNA methylation) is involved in cancer initiation while the increased absorption of DHEA in actively growing cancer reduces DNA methylation.
Tumor suppressor genes are inactivated by DNA methylation. So, low DHEA causes cancer by increasing DNA methylation of tumor suppressor genes. This results in increased cell divisions of the cancer. Cancer exhibits increased hypomethylation.
In my explanation of low DHEA initiation of cancer, I further suggest that, once initiated, cancer begins to use the host's DHEA. This causes cachexia, which I attribute to the loss of DHEA.
It is my hypothesis that evolution selected DHEA because it optimizes replication and transcription of DNA, that is, genes. Therefore, DHEA levels affect all tissues and all tissues compete for available DHEA, especially the brain. (I think evolutionary selection of DHEA produced mammalia. Hormones in Mammalian Evolution, Rivista di Biologia / Biology Forum 2001; 94: 177-184). DHEA naturally begins to decline around the ages of twenty to twenty-five, reaching very low levels in old age. DHEA is also very low in the very young because, I suggest, the brain is using available DHEA for growth and development. As the brain's use of DHEA begins to decline, DHEA levels begin to increase around three to five years of age; this is called adrenarche. When DHEA is low or decreasing, all tissues and genes are adversely affected according to a natural competition for available DHEA between tissues / genes.
It is known that cancer is initiated much more often in the aged. This is due to the natural loss of DHEA of old age. However, it is also known that cancer does not grow as rapidly in the aged. This is due to the reduced DHEA of the aged; the cancer, while taking its DHEA at the expense of the host, is living in an environment of reduced DHEA.