5 ms·

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 associate

by chasil 5y ago

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."

vmception 5y ago
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 5y ago
  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 5y ago
    > 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 5y ago
      > 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/ 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-a-crucial-role-in-immunosurveillance-and-chemotherapeutic-treatment https://www.foundmyfitness.com/episodes/autophagy-and-cancer... https://www.foundmyfitness.com/episodes/cancer-manipulates-systems-autophagy https://www.foundmyfitness.com/episodes/cancer-manipulates-s... https://www.foundmyfitness.com/episodes/caloric-restriction-mimetics-in-aging-improved-cancer-chemotherapy-autophagy-anti-obesity-effect 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 5y ago
    >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/ http://globalcancermap.com/ [.] https://ourworldindata.org/food-supply https://ourworldindata.org/food-supply
    - vmception 5y ago
      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.
- dumb1224 5y ago
  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.
- mlyle 5y ago
  > 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! Actually, you can study these things and see what it does to outcomes, and professionals have. There's benefits from more frequent screening (and harms, too!). The benefits are tempered by a cancer manifesting at stage 4 could mean: * You got unlucky with the screening interval and it showed up inbetween, or * You have a really aggressive cancer that went from stage 1 to stage 4 in a small fraction of the screening interval. The latter is interesting: if you are screening at an interval, the later stage cancers you find are, on average, more aggressive and faster growing. In turn, spotting them earlier doesn't necessarily lead to better outcomes. That is: part of the reason why "finding cancer earlier" is associated with better outcomes is that it's easier to find less aggressive cancers earlier.
  - vmception 5y ago
    That’s an interesting take supporting more screening. Just having more data points for yourself and the collective conscious as well as increasing your luck.
pazimzadeh 5y ago
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).
- sjg007 5y ago
  Elephants have multiple p53 genes. https://www.nature.com/articles/nature.2015.18534 https://www.nature.com/articles/nature.2015.18534
cpard 5y ago
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 5y ago
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.
refurb 5y ago
I’m not sure why it’s a surprise since a good part of cancer is not external factors but just DNA replication alone - there are many correction mechanisms, but they aren’t foolproof. Just being alive puts you at risk for cancer.

by chasil 5y ago

vmception 5y ago

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 5y ago
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 5y ago
  > 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 5y ago
    > 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/ 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-a-crucial-role-in-immunosurveillance-and-chemotherapeutic-treatment https://www.foundmyfitness.com/episodes/autophagy-and-cancer... https://www.foundmyfitness.com/episodes/cancer-manipulates-systems-autophagy https://www.foundmyfitness.com/episodes/cancer-manipulates-s... https://www.foundmyfitness.com/episodes/caloric-restriction-mimetics-in-aging-improved-cancer-chemotherapy-autophagy-anti-obesity-effect 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 5y ago
  >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/ http://globalcancermap.com/ [.] https://ourworldindata.org/food-supply https://ourworldindata.org/food-supply
  - vmception 5y ago
    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.
dumb1224 5y ago
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.
mlyle 5y ago
> 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! Actually, you can study these things and see what it does to outcomes, and professionals have. There's benefits from more frequent screening (and harms, too!). The benefits are tempered by a cancer manifesting at stage 4 could mean: * You got unlucky with the screening interval and it showed up inbetween, or * You have a really aggressive cancer that went from stage 1 to stage 4 in a small fraction of the screening interval. The latter is interesting: if you are screening at an interval, the later stage cancers you find are, on average, more aggressive and faster growing. In turn, spotting them earlier doesn't necessarily lead to better outcomes. That is: part of the reason why "finding cancer earlier" is associated with better outcomes is that it's easier to find less aggressive cancers earlier.
- vmception 5y ago
  That’s an interesting take supporting more screening. Just having more data points for yourself and the collective conscious as well as increasing your luck.

pazimzadeh 5y ago

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).

sjg007 5y ago
Elephants have multiple p53 genes. https://www.nature.com/articles/nature.2015.18534 https://www.nature.com/articles/nature.2015.18534

cpard 5y ago

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 5y ago

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.

refurb 5y ago

I’m not sure why it’s a surprise since a good part of cancer is not external factors but just DNA replication alone - there are many correction mechanisms, but they aren’t foolproof. Just being alive puts you at risk for cancer.