BRCA Mutation, Brest Cancer, Parkinson's, Alzheimer's, and Dehydroepiandrosterone (DHEA)


Copyright 2011, James Michael Howard, Fayetteville, Arkansas, U.S.A.


New information regarding this hypothesis, February, 2013: This is new material regarding how I explain the effects of BRCA mutations on availability of DHEA, at the bottom of this page. With reference to my explanation of how HRT increases breast cancer, “How 'Hormone Replacement Therapy' may Cause Breast Cancer,” at: , the explanation I provide at the bottom may of this page may be involved in how DHEA is reduced, but a new article unites the effects of BRCA mutations directly to my explanation of how HRT lowers DHEA and causes cancer, the link just above. Cancer Causes & Control 2013; 24: 421-426, Kim and Oktay, found that estradiol is increased in BRCA2 mutation carriers. I suggest this increased estradiol causes a decline in available DHEA and, therefore, cancer as described in the link just above.

More new information regarding this hypothesis: The Lancet Oncology 2013: “The sex hormone system in carriers of BRCA1/2 mutations: a case-control study,” (This is a new article at Lancet Oncology; I will complete the citation when page numbers are available: Lancet Oncol. 2013 Nov;14(12):1226-32)

Carriers of BRCA1/BRCA2 mutations are exposed to higher titres of oestradiol and progesterone—known risk-factors for breast cancer. Higher titres of oestradiol in carriers are compatible with this hormone having a role in ovarian carcinogenesis in such women.”

It is my hypothesis of 1994 that low DHEA is the major cause of breast cancer and other cancers (Annals of Internal Medicine 2005; 142: 471-472).  DHEA naturally begins to decline around the ages of twenty to twenty-five, reaching very low levels in old age.  Cancers increase with old age but also grow less well with age.


It is my hypothesis that evolution selected DHEA because it optimizes replication and transcription of DNA.  Therefore DHEA levels affect all tissues because it affects all genes including cancer and cancer genes.  Therefore, when DHEA is readily available, genes will be optimally affected, that is, when DHEA is readily available the differentiated state will be optimally supported.  Cell and tissue integrity rely upon maintenance of the genes which maintain the cell surface.  Participation of a cell within a tissue reduces a cell's surface area and restricts mitosis.  If a cell contains genes of a more primitive state, that is, undifferentiated, then the cell possesses the possibility of inappropriate cell division.  I think low DHEA can allow this possibility to occur.  That is, low DHEA would normally simply reduce a cell's normal activity within a tissue but low DHEA can allow some cells to start cell divisions if the genes of cell division are activated.   Cancers exhibit unrestricted activity of genes of cell division.  This is a simple explanation of how low DHEA may trigger cancer.  (For more detail, please see “Anoikis, Dehydroepiandrosterone, Cancer, and Metastasis,” at: .)


Following growth and differentiation, genes are presented with levels of DHEA available as a combined consequence of reduced cell surface areas and competition between the various tissues of the body.  Therefore, the activity of genes will follow the levels of available DHEA.  When we are young, high DHEA results in optimal gene function.  Therefore, aging results in reduced gene function and this will result in reduced gene function.  Since genes are affected by mutations, some genes will be optimally active and some will be less so depending upon the degree of mutation.  Therefore, as DHEA declines, some genes will simply exhibit reduced function while others will exhibit reduced function according to their structure.


I suggest the foregoing explains why some people do not exhibit Alzheimer's, Parkinson's, or the other disorders of the brain during aging while some exhibit varying degrees of these disorders.  Since DHEA declines with age, intact genes will persist in function more than genes which are variously, adversely formed. 


It is known that AD, Parkinson's, etc., exhibit “early onset” in some individuals.  I suggest these individuals possess genes which are so abnormal that their function is adversely affected early in the decline of DHEA.


As noted in the beginning of this treatise, I think breast cancer is a disease caused by the decline of DHEA exposing oncogenes.  This will produce a continuum very much like the brain disorders described above.  The genes BRCA1 and BRCA2 are known to produce early onset breast cancers in  women who possess these genes.  I suggest these genes act in the very same manner as early onset genes in the brain disorders.  That is, I think BRCA1 and BRCA2 are genes which become activated by the early decline of DHEA.  Since these breast cancers are activated early in the decline of DHEA, they will be more active cancers because they have access to increased DHEA of early aging compared to the low DHEA of old age.  That is, cancers of younger age, once activated, will grow more rapidly because of increased DHEA.  As these cancers, and cancers of old age, use DHEA for their growth, these cancers take DHEA at the expense of other tissues.  This also explains the severe effects of cancer on the body called “cachexia.”