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 )
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.
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.
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