An Explanation of Cancer and the Increase in Cancer: High Testosterone, Low DHEA and Breast Cancer
Copyright ã 1994 James Michael Howard.
This
is mentioned in International Journal of Cancer
2005; 115: 497 and Annals of Internal Medicine 2005; 142:
471-472, my publications.
New supporting material is below.
Sometime in the early 1990's, I developed my hypothesis that low dehydroepiandrosterone (DHEA; the major adrenal hormone) may trigger cancer. I sent this idea to a number of publications, including the Journal of the National Cancer Institute, April 11, 1994. However, prior to that, I had the following "letter to the editor" printed in The Morning News of Northwest Arkansas, March 14, 1994, page 4A. This briefly explains my explanation of cancer and low DHEA. I used the increase in breast cancer to explain this. (You should note that a connection of high testosterone and low DHEA had been noticed some time prior to my explanation. However, no one, other than I, has produced an explanation of how this combination of hormone levels could trigger cancer. I was not aware of the early findings of high testosterone and low DHEA when I developed my idea.) The Letter to the News:
"During the past year, a lot has been published about
increased cancer in this country. When this controversy began a few years back,
it was refuted; the increase was attributed to better detection.
Epidemiologists have now proven the increase is real. To account for this, some
investigators at N.I.H. say the rise is caused by cancer-causing chemicals in
the environment. One of the chief supporters of this idea, however, suggests
these chemicals may account for only a minor part of the increase in cancer. I
suggest the majority of the rise in cancer results from the same mechanism that
produces the 'secular trend.'
The secular trend is an increase in body size and earlier
puberty in boys and girls with each generation. I suggest the trend results
from increases in numbers of individuals of high testosterone, male and female.
(Testosterone is not 'the' male hormone, males simply produce more.
Testosterone increases size, aggression and sexuality in both sexes.) Males and
females of higher testosterone arrive at puberty earlier and are more sexually
active; they make more babies than low testosterone couples. The increase in
cancer directly parallels the secular trend, that is, the increase in
percentages of higher testosterone individuals. The best way to see this is in
females. Breast cancer in females also parallels the secular trend, and early
puberty is a key risk factor in female breast cancer. The simple answer is that
testosterone advances old age, and breast cancer is mainly a phenomenon of old
age.
My work suggests all gene activity requires [is optimized
by] the hormone, DHEA. That is, all genes compete for DHEA. DHEA is produced in
a limited supply during the life-span and naturally begins to decline around 28
years old. Therefore, I suggest loss of DHEA results in aging. Testosterone
increases use of DHEA for 'testosterone-target' genes. Increased testosterone
increases use of DHEA for these genes, that is, their tissues. This means that
testosterone increases use of DHEA and advances the time when DHEA begins to
decline. Testosterone advances aging. This is why men die, on average, earlier
than women.
I suggest 'embryonic' or 'growth type' genes are activated
when DHEA is readily available, and 'tissue type' or 'adult type' genes are
activated by less DHEA. As we grow, overall DHEA availability is reduced
because of our tremendous, early growth. As overall DHEA is reduced, tissues
begin to form at the expense of growth. The ratio of growth genes changes as
tissues begin to form. That is, the ratio changes from more growth to more
tissue formation, and this continues until around age 28. At this time, tissues
begin to experience reduced DHEA. Tissues begin to age. My work suggests this
causes a few cells to reverse their ratio of DHEA availability. That is, some
revert to embryonic type cells which grow rapidly.
Rapidly growing, normal embryonic cells and cancer cells
have few 'cell adhesions.' Cell adhesions stick cells together; the more a cell
has, the less free surface area it has to absorb DHEA,
from blood. As cell adhesions form, the reduced DHEA pushes the cell toward the
tissue ratio. (Most tissues are groups of cells literally stuck together for a
unified purpose.) Loss of cell adhesion is characteristic of cancer cells. I
suggest loss of cell adhesions increases the free surface area of cancer cells,
and, therefore, increases their ratio of DHEA. This increased DHEA would then
activate rapid cell growth, that is, it would activate 'embryonic type' genes
in cells which absorb large amounts of DHEA. These cells would form tumors
because of their rapid growth and increased absorption of DHEA.
Therefore, if I am correct, breast tumor tissue should
absorb DHEA more rapidly than other tissues at the expense of DHEA in the rest
of the person. It is known that breast tumors, but not normal breast tissue,
concentrate DHEA (Journal of Steroid Biochemistry 26: 151, 1987).
Measurable levels of DHEA are reduced in women with breast cancer, and this
reduction in DHEA occurs as early as nine years prior to diagnosis (Geriatrics
37: 157, 1982). Once the breast tumor has begun to grow, it uses DHEA at
the expense of the rest of the body. This severe loss of DHEA, caused by the
cancer, will than advance aging in the rest of the body. I suggest this causes
the wasting syndrome, called cachexia, seen in breast cancer, and other cancer,
victims."
End of the Letter to the News
I suggest that low DHEA triggers oncogenes in people who have them, and this is why cancer is more common in old age. According to my work, all tissues, including cancers, must utilize DHEA for growth. Since DHEA is reduced in old age, this also explains why cancers, though more common in old age, grow less rapidly in old age. If proper DHEA levels prevent cancer, then DHEA should prevent cancers induced by known carcinogens. This has been determined in number of studies, such as "Exceptional Chemopreventive Activity of Low-dose Dehydroepiandrosterone in the Rat Mammary Gland," Cancer Research, 1996; 56: 1724. So, the commonality of depression and cancer is low DHEA.
In 2002 and 2003, my connection of testosterone with breast cancer was supported: "testosterone might be more strongly associated with [breast cancer] risk than estradiol" (Journal of the National Cancer Institute 2002; 94: 606-616). "The estimated relative [breast cancer] risks between upper and lower tertiles were 2.07 (95% confidence interval [CI] 0.97-4.41) for estrone in postmenopausal women, 2.01 (95% CI 0.96-4.21) for testosterone in premenopausal women, and 2.40 (95% CI 1.11-5.21) for testosterone in postmenopausal women, after adjusting for age at first live birth, waist-to-hip ratio, total calorie intake, a history of fibroadenoma, a family history of breast cancer and SHBG." (International Journal of Cancer 2003; 105: 92-7).
Here is the new material:
Two articles add support to my hypothesis
regarding testosterone in women and breast cancer. That is I suggest increased
testosterone is involved in triggering cancer. In the first article from the
January, 2004, Journal of the National Cancer Institute, U.S.A., you
will read the finding that "active smoking may play a role in breast
cancer etiology." The second article demonstrates that smoking in women is
connected with increased testosterone. "Current smokers had the highest
testosterone concentrations with decreasing values in former and nonsmokers (p
= 0.0001)." (The abstracts of these two articles are available at my
explanation of breast cancer; click on the link.) Again, I suggest this adds
support to my explanation of the mechanism of cancer.
Smoking is connected to breast
cancer:
"Background: There is great interest in whether exposure to
tobacco smoke, a substance containing human carcinogens, may
contribute to a woman’s risk of developing breast cancer. To date,
literature addressing this question has been mixed, and the question
has seldom been examined in large prospective study designs. Methods:
In a 1995 baseline survey, 116 544 members of the California
Teachers Study (CTS) cohort, with no previous breast cancer
diagnosis and living in the state at initial contact, reported their
smoking status. From entry into the cohort through 2000, 2005 study
participants were newly diagnosed with invasive breast cancer. We
estimated hazard ratios (HRs) for breast cancer associated with
several active smoking and household passive smoking variables using
Cox proportional hazards models. Results: Irrespective of
whether we included passive smokers in the reference category, the
incidence of breast cancer among current smokers was higher than
that among never smokers (HR = 1.32, 95% confidence interval [CI] =
1.10 to 1.57 relative to all never smokers; HR = 1.25, 95% CI = 1.02
to 1.53 relative to only those never smokers who were unexposed to
household passive smoking). Among active smokers, breast cancer
risks were statistically significantly increased, compared with all
never smokers, among women who started smoking at a younger age, who
began smoking at least 5 years before their first full-term
pregnancy, or who had longer duration or greater intensity of
smoking. Current smoking was associated with increased breast cancer
risk relative to all nonsmokers in women without a family history of
breast cancer but not among women with such a family history. Breast
cancer risks among never smokers reporting household passive smoking
exposure were not greater than those among never smokers reporting no
such exposure. Conclusion: Our study provides
evidence that active smoking may play a role in breast cancer
etiology and suggests that further research into the connection is
warranted, especially with respect to genetic susceptibilities."
Journal of the National Cancer Institute, Vol. 96, No. 1, 29-37,
January 7, 2004
Smoking is connected to increased
testosterone in women:
"While there is substantial evidence of
the importance of endogenous and exogenous estrogen in reproductive health and
chronic disease, there is little consideration of androgens in women's health.
In the Michigan Bone Health Study (1992-1995), the authors examined the
correlates of testosterone concentrations in pre- and perimenopausal women
(i.e., age, menopausal status, body composition, and lifestyle behaviors) in a
population-based longitudinal study including three annual examinations among
611 women aged 25-50 years identified through a census in a midwestern
community. Current smokers had the highest testosterone
concentrations with decreasing values in former and nonsmokers (p = 0.0001).
Body composition measures (body mass index, body fat (%), weight (kg), lean
body mass (kg), and fat mass (kg)) were significantly and positively associated
with total testosterone concentrations in a dose-response manner. Hysterectomy
with oophorectomy was associated with significantly lower testosterone
concentrations. Alcohol consumption, physical activity, and dietary
macronutrient intake were not associated with testosterone concentrations. This
is one of the first studies to examine correlates of serum testosterone
concentrations in anticipation of the growing interest in the role of androgens
in women's health. The greater circulating levels of testosterone in obese
women and smokers suggest that testosterone concentrations should be considered
in the natural history of disease conditions where obesity and smoking are risk
factors, including cardiovascular disease." American Journal of
Epidemiology 2001 Feb 1; 153(3): 256-64