Wednesday 4 November 2015

human biology - Extremely rare occurence of Heart cancer?


The occurrence of Heart cancer (similar, but not the same as Rhabdomyosarcoma) is extremely rare, about 1 per year according to MayoClinic. The reason for this rarity is explained to be the post-mitotic nature of cardiac muscles. Since they stop dividing early in the life cycle of humans and grow only by increasing in volume, they are very less prone to oncogenic activation events caused due to mutation as a result of an error in DNA replication (since they do not replicate their DNA as they do not divide).


Although I am not an expert in tumours and cancers, I think that malignant tumours in nervous tissue, i.e. brain tumours are fairly common, at least more common than heart cancer by several orders of magnitude. But neurons constituting these tissues are also permanently in interphase and hence do not divide. Moreover, secondary malignancies in Brain and nervous tissue is also much more common than secondaries in heart (rare) though metastatic secondary tumours, I believe, do not require oncogenic transformations in the host tissue. A metastatic fragment of a primary malignancy transported by blood is enough to cause secondary tumours.


How then these tumours (primary and metastatic-secondary) are more common in nervous tissue than heart, though both are post mitotic, i.e. permanently in interphase?


Here and here are a few links which give some basics of cardiac malignancies, though they don't address the question quite directly. The study here provides possible explanation of lack of cancer due to high oxygen content.



Answer




This is a specific version of the great cancer question: "Why are some cancers more common than others?" The answer is either "Some have more common causes", and (or) "Some are cured spontaneously more often". So now all you are asking is "What causes cancer?" and "How do we cure it?"


Given that, I don't expect a general definitive answer will be forthcoming. A specific answer might be possible, but I doubt there will be any existing experiments that address this. With the obvious caveat that only experimental or statistical results can really answer your question, here are a couple of off-the-cuff hypothesis for consideration:


1 - Differences in stem cell populations.


Apparently, differentiation can actually be targeted as part of a treatment in some neuroblastoma cases - see the section on "Differentiation therapy" in this page from Sloan-Kettering. Cardiac stem cells seem to exist, but a difference in relative population and turnover rates between brain and heart might be related to the relative frequencies of these types of cancers. @WYSYWIG referred to neural progenitors in his comment above.


2 - A filtering effect due to a more extreme selection pressure in the uniformly stressful environment of the a beating heart.


Although there is a relation between elevated levels of oxidative stress and cancer causing mutations, it could be that this only matters in a punctuated stress environment, where cells have down time to recover. A sustained stress environment might actually helps prevent cancer. The path from normal to cancer cell requires multiple mutations, and I would not expect most pre-cancerous cells to be more fit than correctly wired ones. The extra stress of the cardiac environment might produce an elevated mutation rate, but also produce an even higher rate of apoptosis in early "sick" cells before they accumulate enough mistakes to become become cancerous, resulting in a net decrease in the rate of cancer.


Both of these ideas fit with heart cancer being less common and with metastasis from elsewhere being more common in heart than primary cancer, but unfortunately, a higher rate of clearing of sick cells would necessitate a higher rate of replacement from stem cells, so these two hypotheses partially cancel each other. Again, hypotheses without experiments are not really answers.


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