The long, slow process of carcinogenesis
science.org
science.org
"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."
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).
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.
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
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.
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
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.
I don't think I'm compelled to provide that but I'm open to counter theories
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"
It would be but it's so, so, ever so hard, to go without even one single meal.
I've stopped evangelizing "fasting" or even shorter intake windows.
If you can't be bothered to skip breakfast for a few weeks just to see how your body responds then let's stop wasting our time and just talk about football or something.
... how 'bout them Cowboys ?!
Huh? You'd be surprised...
But I know a lot of people who cannot skip a single meal and get irritated or angry.
I think they just need to get used to some poverty for a while.
(Of course, it's not that black&white, and not eating at all will quickly deteriorate your health -- I'm just saying that hangriness is not the same as hunger, and learning to differentiate between the two is important)
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.
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).
Just being alive puts you at risk for 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.
Shouldn't we have an assembler, compiler, and linker by now? What's taking so long?
It's like trying to understand Linux from just looking at the /bin directory. Simply having the executables tells us very little about the system as a whole.
Newer treatments might actually be worse, but early diagnosis makes them look more effective.
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.
...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.
No one argues this is true. But there's mounting evidence that this is less true than one would have believed a couple of decades ago.
* First, as the parent to your post says: if a cancer takes 3 years to go from stage 1 to stage 4, detecting the cancer at stage 1 will increase measured survival by 3 years even if your treatments do nothing.
* Second, the stage at detection is also a measure of how aggressive the cancer is. That is, if you screen every year, and find 100 stage 4 cancers and 100 stage 1 cancers in your population... odds are the stage 4 cancers are much faster growing and more likely to become malignant. You didn't necessarily find them "earlier".
Maybe it's stage 1 because you got lucky and saw it early. Maybe it's stage 1 because it grows really slowly and will be stage 1 still in 5 years.
Only way you could know is to not treat and watch what happens... Everything else is a fudge.
That being said my family has started to wonder, "when did he first get sick?" as he seemed relatively well until early last year -- other than his other conditions. The best we can come up with is "about a year ago". But looking at this it may have much much earlier. It probably wouldn't have changed the treatment or outcome, 87 is a hell of a run, but from an objective point of view it's very interesting to try to understand when this terrible thing first saw its genesis in him.