[HN Gopher] The long, slow process of carcinogenesis ___________________________________________________________________ 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. ___________________________________________________________________ (page generated 2022-01-20 23:00 UTC)