[HN Gopher] The long, slow process of carcinogenesis
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The long, slow process of carcinogenesis
Author : _Microft
Score : 98 points
Date : 2022-01-20 17:43 UTC (5 hours ago)
(HTM) web link (www.science.org)
(TXT) w3m dump (www.science.org)
| fabian2k wrote:
| I remember reading the chapter on cancer from the Alberts
| "Molecular Biology of the Cell" and even though I understood the
| basics of cancer at that point I was still suprised by many
| aspects. I didn't expect just how messed up the genome of cancer
| cells could be, with chromosomes fusing or duplicating. Of course
| these kind of extreme changes are very often lethal to the cell,
| but in the cases where they aren't they also provide the base for
| breaking enough control mechanisms that would otherwise prevent
| cancer.
|
| Most cancer cells are genetically unstable, some mechanisms that
| usually reduce mutation rates are broken in them. And this
| enables them to accumulate the mass of mutations they need to
| actually become cancer.
|
| The most striking hypothesis I read in that chapter was that
| telomere shortening could actually help a cell to become
| cancerous. I've no idea whether that idea help up, but it was
| pretty much the opposite of what I expected. The basic idea is
| that for cells that have a way to evade the usual stop of cell
| division for short telomeres, this becomes an advantage. The
| cells still divide, shortening telomeres so much that it
| destabilizes the genome. If the cell can survive that, it gains a
| large amount of the kind of genetic instability that is needed
| for it to become cancerous.
| asdff wrote:
| A big issue is turning on things that shouldn't be turned on. A
| good way to imagine the chromosomes is like they are
| independent scripts with blocks of code. Some of the code is
| functional, some of it is code rot that is best left commented
| out. When you get a mutation that breaks the processes keeping
| the integrity of this codebase together, you end up sometimes
| seeing chunks of code cut and pasted around where it shouldn't
| be. Chunks fused together or separated, inverted, duplicated,
| removed entirely. This might result in code that should
| normally be commented out becoming uncommented and causing a
| lot of harm to the host.
| hotpotamus wrote:
| This comment reminds me of the first time I saw genetic code
| in github and realized that the analogy of computer code to
| genetic code is almost not an analogy because on some level
| they're the same thing. I find it interesting but
| uncomfortable.
| agumonkey wrote:
| code but we don't have the interpreter figured out yet
| m_fayer wrote:
| The thought that makes me most uncomfortable is the idea
| that we're reading code written by a dumb process, not a
| living thing. Dumb physical processes shouldn't be able to
| compose anything. It's like we broke into the universe's
| private files and found an infinity of insane scribbling,
| about us. It's uncanny.
| VeninVidiaVicii wrote:
| There's a related problem when you can diagnose a cancer really
| early -- it's that you wind up, technically, living with cancer
| for a longer time. Early diagnosis makes treatments look like
| they're working better and better, when they might not be.
|
| Newer treatments might actually be worse, but early diagnosis
| makes them look more effective.
| est31 wrote:
| The rule of thumb with cancer is that the earlier you diagnose
| it, the more treatable it is. So yes, please detect cancers as
| early as possible.
| the_af wrote:
| I don't have a firm opinion but tend to agree with you,
| _however_...
|
| ...an article linked to here on HN many years ago argued that
| sometimes early detection can lead to downgraded quality of
| life. The examples they provided were of middle-age men
| diagnosed with very early stage prostate cancer, which
| sometimes led to surgery with debilitating complications
| (like erectile dysfunction, incontinence, and others). The
| article argued many of those cancers were effectively
| harmless, that those men would have died of something else
| after a long life without ever realizing they had cancer, and
| that the treatment was considerably worse than the disease.
|
| Of course, it could be argued that knowing is always better:
| that the mistake in those cases was to perform unnecessary
| surgery.
| nradov wrote:
| Almost every elderly person has cancer. It's just that many
| people die from something else first before those tiny
| malignancies grow large enough to cause significant clinical
| symptoms.
| inglor_cz wrote:
| Cancers are very diverse in this regard.
|
| Prostate cancer is quasi-normal in men over 70 and usually
| grows so slowly that it does not influence their lifespan.
|
| Pancreatic cancer is deadly at any age and its treatment
| would profit a lot from very early detection.
| cbsmith wrote:
| Except when you are analyzing treatments, you would want to
| control for when & how the diagnosis was made...
| bitL wrote:
| How about taking DCA 300-1000mg/day as a prophylactic? Are there
| any trials on that?
| xyzzy21 wrote:
| This is why you really need FDA testing of ANYTHING to be carried
| out over years to decades.
| kmonad wrote:
| That does not follow in any way, and is just plain wrong.
| The_rationalist wrote:
| chasil wrote:
| Well, this is a surprise:
|
| "Using rates of mutation as a clock, some of them appear to go
| back _even to before birth_ - the key JAK2V617F mutation, long
| associated with these malignancies, is estimated to have shown up
| anywhere from the 33rd week of gestation up to the age of 11. The
| DNMT3 mutation, similarly, seems to have appeared from the 8th
| week of gestation (!) out to about the age of 8. "
| cpard wrote:
| This is insane. Both my mother and grandmother died because of
| myelofibrosis. My mother was suffering with related diseases
| for almost 15 years before they diagnosed the symptoms as
| myelofibrosis and after that doctors where still debating if
| the disease was there since the beginning or not
| possibleworlds wrote:
| My two sisters and I all have diagnosed Polycythemia Vera with
| the JAK2 mutation present. Neither parent have the mutation or
| the disease. From what I understand PV is not supposed to be
| hereditary and clusters like ours are very rare. In retrospect
| the earliest signs (at the time slightly elevated platelets)
| were present for me when I had a very bad bout of Epstein-Barr
| in my early 20s and was getting regular blood counts done for
| months, although the first diagnosis wasn't picked up until my
| eldest sister was in her early 40s and the disease was non-
| trivially advanced.
| pazimzadeh wrote:
| Not too surprising in theory. During development, the body
| requires very fast growth. Very fast growth increases the
| chance of mutations.
|
| If the selective pressure to develop quickly diminishes, then I
| would expect that uncontrolled growth (cancer) would be less
| likely as well. It would be interesting to see if this is
| observable in other animals (those with the shortest
| development times, which require the fastest bursts of growth,
| should be at higher risk for cancer or should have evolved
| solutions like extra telomerases).
| vmception wrote:
| That is surprising.
|
| One of the frustrating things about cancers is that nobody
| knows the cancer's growth rate, how long from stage 1 to stage
| 2 etc, when in reality they are just categories, aka "if you
| have cancerous cells from your liver in your neck, then its
| stage 4". The problem with this is that no interval of
| preventative testing can be rationalized. You don't know if
| once a decade, or once a year, or using your privilege to get
| tests every 3 months would yield any help in early detection at
| all! The medical professionals don't know either. "Cancer" is
| obviously too broad, but even if you have a history of a
| particular type of cancer in your lineage, you're still at the
| same issue. We don't know if one cell flips to cancerous and
| defeats your body's defenses for reproduction all the way to
| stage 4 within 2 weeks, or whether it is over years.
|
| Knowing that the contributing mutation can be 30-50 years prior
| is really helpful, and can help doctors authorize the use of
| their medical facilities more pointedly, while researchers
| continue to isolate and make peer-reviewable preventative
| measures that the holistic naturopaths can never do (because
| they don't do peer review, there may and has been accidentally
| salvagable parts of their form of medicine).
| chasil wrote:
| I think that finding a cancerous liver cell in your neck
| means metastasis is happening, and the slow process is
| assumed to be complete. Unless the immune system is attacking
| these cells and their numbers are controlled, this would be
| stage 4 (while I am not a physician, let alone an
| oncologist).
|
| I think that the best weapon that the general public has
| against cancer is autophagy, triggered by keeping blood
| glucose very low at least some of the time. Metabolic changes
| that can awaken apoptosis might kill many of these mutation
| carriers.
| vmception wrote:
| > I think that finding a cancerous liver cell in your neck
| means metastasis is happening, and the slow process is
| assumed to be complete.
|
| To me thats what I said, that's what stage 4 means,
| metastasized.
|
| > I think that the best weapon that the general public has
| against cancer is autophagy
|
| One can wish
| TedDoesntTalk wrote:
| > One can wish
|
| It's not really a wish anymore. There are studies showing
| this, but I'm too busy to find them for you. Rhonda
| Patrick at https://www.foundmyfitness.com/ has interviews
| with various researchers on this topic. Here are some,
| but this is by no means exhaustive:
|
| https://www.foundmyfitness.com/episodes/autophagy-and-
| cancer...
|
| https://www.foundmyfitness.com/episodes/cancer-
| manipulates-s...
|
| https://www.foundmyfitness.com/episodes/caloric-
| restriction-...
|
| My layman understanding is that healthy cells can
| withstand the rigors of fasting and fasting-mimicking,
| but many cancer cells cannot. They die.
| Jimmc414 wrote:
| >I think that the best weapon that the general public has
| against cancer is autophagy, triggered by keeping blood
| glucose very low at least some of the time. Metabolic
| changes that can awaken apoptosis might kill many of these
| mutation carriers.
|
| Since fasting is the best way to induce autophagy, that
| could explain the apparent negative correlation between
| cancer rate and a country's food supply [.]
| http://globalcancermap.com/ [.]
| https://ourworldindata.org/food-supply
| vmception wrote:
| no, thats explained at how young people die, also related
| to a country's food and water supply
|
| Africa's average age is half of North America's, and
| after controlling for infant mortality still so few other
| people make it to the much higher life expectancy limit
| (which is still 10-15 years lower than North America)
| there that there isnt opportunity for cancer diagnosis to
| rear up as often! Let alone be tested for cancer to
| understand if that was an ailment or contributing
| comorbidity.
| appletrotter wrote:
| Makes sense, but can you prove it?
| vmception wrote:
| which parts? you really want me to provide sources on
| average age as well as life expectancy? you don't know
| the accepted consensuses on why societies in the
| continent of Africa operate in abysmal conditions to
| support human life uninterrupted?
|
| I don't think I'm compelled to provide that but I'm open
| to counter theories
| appletrotter wrote:
| The counter theory is the comment that OP made. Your
| response opens with a denial of OPs theory; this response
| would be more effective with citations. Your theory makes
| sense, but I just don't see why it has to be mutually
| exclusive. Maybe they're both factors to varying degrees?
| vmception wrote:
| sure, I can accept a multipronged explanation, I already
| acknowledged that both of our observations are related to
| the food supply issues chronic on that continent, I don't
| think their specific correlation has been studied though
| so there's nothing to really say. My hypothesis is that
| my observations (which have been studied and are actively
| being addressed by many organizations) are going to have
| a greater weight by mere deduction: there is nothing
| unique enough about people in Africa that would make
| cancer appear earlier, and since they die earlier there
| and have worse preventative treatment to know other
| upcoming ailments, the cancer wouldn't come up because
| they're already dead from other basic infrastructure
| issues.
|
| What I'm reading is "hey here is this ailment people get
| in their 60s, here's this continent where people barely
| survive until their 60s, do you have a citation for why
| people there don't frequently get that ailment there? we
| should really study that"
| dumb1224 wrote:
| I'm not a cancer biologist but I work in the field of
| supporting cancer research and targeted therapy. My naive
| take is: the type of mutation and its effect on cancer
| progression is still being studied heavily. A lot of the
| understanding of biological pathways and functional impacts
| of these mutations are being updated and very conservatively
| corrected. From a systems biology point of view, the whole
| body is so mechanistically complex in its response to
| environmental and internal stress that it's a bit difficult
| to predict outcome / prognosis. Important cancer pathways are
| well studied and are usually involved in disease progression
| but it is still very tissue type / biomarker categorisation
| specific. The real driver mutations are being discovered for
| each cancer type but the ultimate goal is be able to see the
| big picture.
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