The JAMA article suggested that there was significant
increase in the number of breast cancer cases between 1976 at 1.53 to 2.8 per
100,000 in the 18-34 year old female population. And to boot the cancers were
more aggressive and fatal!
That got me thinking…
This entire DNA enterprise is a remarkable creation! From
the rudimentary beginnings with just four Nucleic acid molecules to this giant
skyscraping intelligence called human. What a concept?
It is well know that older women who gat breast cancer have
the slower tumor growth rates. These cancers are universally limited in their
scope of aggression. The disease is mostly discovered in the breast (Stage I or II) with some cases
spreading to the lymph nodes in the axillary region (Stage II or III) and fewer
still traversing through the blood vessels and finding haven in distant organs
(Stage IV). (you can read some more here: http://jedismedicine.blogspot.com/search?q=breast+cancer+energetics
)
Why the slow pace in the elderly?
For that answer we have to go into the evolutionary dynamics
of cancer in the elderly. As humans we are subject to about 10,000 hits on our
DNA per day. These hits come from the atmosphere in the form of errant gamma
rays or even neutrinos (although some claim they just pass through).
The damage
done to the DNA causes a disrupted DNA code in the form of an error, a
“missense” or “nonsense.” The mismatch repair gene is, by virtue of its great
“proof-reading” abilities, able to repair the damage as if no damage had ever
occurred, like sifting “squares” through round holes. The hits however keep
coming and most time the DNA damage is in non-critical area where the change
just exists without repair as a SNP (Single Nucleotide Polymorphism) or as a
“snippet.” Other times the degraded gene is optimized by epigenetic phenomena
that can modulate the behavior into compliance, even though the mutated gene
persists and still other times through the evolutionary leap of the
Transposons; Barbara McClintock’s “jumping genes” the DNA itself in self
preservation wants to thwart a potential risk to it, like the sickle cell gene
as an affront to Malaria. But let me stay on message here… (you can read some
more here: http://jedismedicine.blogspot.com/2011/02/human-diversity-in-genes.html )
Aging
The problem as we age is one of capabilities. Just like at
70 you cannot jump like you used to, or quickly pick up an object on the
ground, as you did when you were 20 years old. The Mismatch repair gene cannot
keep up with the accumulating DNA damage either. Thus the damaged erroneous
gene through a mistimed event when the mismatch repair gene is not looking or
able, gets transcribed into the dividing cell and that cell through the
transcriptional powers of an unleashed cancer promoter gene or by virtue of
damage to the tumor suppressor gene, leads to cancer. The process is slow; the
aging process retards the cellular division, hence the growth rate is also
slow. However over time as more and more unwanted genetic mutations gather
forces within the cell, an explosive all out head for the hills growth spurt
occurs culminating in the somatic death. Then there is also the Telomere issue.
A finite number of these CAG units exist in the cellular DNA; tiny fragment
repeats at the 5-prime ends of the DNA. Each repeat unit is discarded with each
division and after the last one is used up the cell division fidelity is no
longer guaranteed. Remember the Hayflick Limit? (1) A fibroblast in culture
medium will only grow for a certain number of divisions and then no more. Well
same here in the human body! With no further division the cells eventually die.
Unless of course you happen to sprinkle a little Telomerase enzyme and the
cells happily continue to divide. Now guess who has a boatload of Telomerase?
You guessed it, the cancer cell! (You can read some more here: http://jedismedicine.blogspot.com/2012/06/aging.html?spref=tw )
The normal cellular division rate in the young however is
robust. Their mis-match repair is in great shape, they have plenty of the CAG
repeats on their DNA and life is humming along. New cellular structures are
needed to add to the existing ones as the genetic structure commands the
proteins to build and strengthen the scaffolding and the organ function for the
present and the future life span. This growth rate is noticeable in the height,
weight, body structure, physical and mental reserves and all the fine things
that adolescent and young adults are heir to, albeit without knowing or caring
about it. Since billions of cells in this multi-trillion-cell economy are in a
state of division, so also is the mismatch repair gene mechanism in full dress
rehearsal. The functionality of the repair mechanism and the governance of the
p53 guardian both keep the harmonious fidelity of normal information transfer
from the mother cell to the two daughter cells. Growth is a natural byproduct
in youth.
p53 Guardian of the Genome
Now stay with me on this one.
The Disposable Soma theory states that the human body is just a vessel
to transfer and propagate information to the progeny. In other words, the DNA
is the real information and the body is just a glorified medium for the
transport and transfer mechanism. So if that premise is correct and it seems to
be relevant, then maximum fidelity is needed at a young age, which is true.
After the 60 years have walked the road of life, is where cancer starts to
raise its ugly head at a faster incident rate, doesn’t it?
If cancer was affecting the youth at
the same rate as it does the elderly, then the human population would be
stifled and ultimately go extinct. Now wouldn’t it? The self preserving
abilities keep the youth from being endangered so that the propagation of life
may continue unabated. Each progeny is therefore blessed with an evolutionary
benefit based on the attached Lamarckian nurturing benefit.
Disposable Soma Theory
So you might think that this is counter to the premise
stated above. But bear with me, on this burden of reason. Imagine that the most
important mechanism is for the DNA to transcribe its information with the
utmost of fidelity and then an erroneous gene (mutated) escapes the mis-match
repair mechanism and the p53 governance, what is the soma to do? What is the
DNA to do? If the DNA continues to propagate the bad genetic structure it will
perpetuate a somatic vessel that is ill-equipped to propagate it’s progeny and
the population will die. In other words a faulty gene that forces the soma into
extinction, is also forcing itself to the same fate. So what mechanism does the
DNA have in its quiver?
That is where the dilemma exists.
The only mechanism for the DNA is to allow the propagation
of the mis-wired genetic complex to complete its task of allowing the cancer to
grow unchecked and unabated, quickly and efficiently, so that future damaged
genes are not created in the process through mating and to therefore keep the
fidelity of the ancient DNA structure in place that has allowed humanity (from
Homoerectus to now) to survive for millions of years.
From
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to
Equally in men with testicular cancer who have borne
children there is a high propensity for their wives to miscarry. The primary
directive of fidelity is at stake and the DNA does not wish to have a progeny
that will be unable to propagate fully with purpose.
So the basic premise is that in younger women given such a
DNA damage (from random DNA hits and lifestyle choices etc.) of the mismatch
repair gene efforts and the p53 governance, once the data is error prone the
quick, expansive growth rate and the rapid doubling time of the cells leads to
an aggressive metastasizing cancer.
So, why the fast spread? That too, is as a result of the
accumulating gene mutations. Once the bad cell has transgressed the imposed,
self-governing limits, it is free to churn and burn any and all encoded
messages within (acquiring the H-ras gene for instance) . Having this lack of
governance and ability, predisposes it to acquire mechanisms that thwart the
immune surveillance and the spread comes fast and furious. The cancer cell now
is on a quest for its own short-lived dominance!
Thought experiment is over.
I know, I know, there will be vilification, demonization and
all the rest because these are not politically correct, soothsaying words. Rest
assured, if another mind catches the drift of this reasoning, solutions to this
problem might come in the future. If you reached here and stuck with my
monolog, I thank you.
References:
Hayflick L, Moorhead PS (1961). "The serial cultivation
of human diploid cell strains". Exp Cell Res 25 (3): 585–621.
Rebecca H. Johnson, MD; Franklin L. Chien, BA; Archie
Bleyer, MD. Incidence of Breast Cancer With Distant Involvement Among Women in
the United States, 1976 to 2009. JAMA. 2013;309(8):800-805.
doi:10.1001/jama.2013.776.
EDITORIAL: Testicular cancer and infertility
BMJ 2000; 321 doi:
http://dx.doi.org/10.1136/bmj.321.7264.781
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