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Comment by jszymborski | Hacker News Reader

As a person who studied cancer, I am probably not this article's audience.

That said, I feel the need to point out that chronic inflammation has long been known to be one of the roots of cancer. Chronic inflammation can be caused by a few things but common among them is the immune system.

The framing of the article, in my quick skim, felt like it was insinuating that researchers believed that cancer arises from mutations alone, and that everyone assumed carcinogens were all mutagens.

I haven't read the paper this article is describing. It seems very interesting. But the headline and the article makes it seem like some major turning point or ground shift which IMHO it is not.

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And are we sure inflammation is the root cause and not just a bystander? Couldn’t it be pathogens that are kept in check by inflammation, which then also cause cancer to develop? HPV and papillomas, and H. pylori and stomach cancer have been such findings. Apparently, sometimes cancer cells contain fungal DNA (not well studied though, could be contaminants as well).

Edited the last sentence.

Probably not, given the multiple conditions that are "sterile" inflammation that lead to neoplasms. Consider the example of asbestos; the particles lodge in the lungs which lead to a robust immune response that attempts to clear it, which has a strong association with the development of lung neoplasms. I'm not aware that the link between the inflammation and the development of the neoplasm is well understood. Autoimmune diseases and chronic GERD are other examples.

Can you provide more context on what question you were addressing? I‘m not sure what point you are making here.

>Couldn’t it be pathogens that are kept in check by inflammation, which then also cause cancer to develop?

In reference to this question. These conditions with prolonged inflammation lead to cancer in the absence of a primary pathogen.

>Apparently, sometimes cancer cells contain fungal DNA (not well studied though, could be contaminants as well).

In reference to this, if you are referring to the "tumor microbiome" hypothesis, it has been thoroughly debunked.

http://dx.doi.org/10.1128/mbio.01607-23

> in the absence of a primary pathogen

And how can absence of a pathogen be determined, in vivo? That sounds a bit overconfident in current tools, no? H. pylori apparently can hide inside Candida cells. Biofilm lets pathogens prosper while hiding them from diagnosis. Who knows what else is going on.

I don’t think the microbiome hypothesis can be rejected at this point. Studies were flawed, yes.

I personally am not a fan of the status-quo-ism that comments such as yours express. There’s so much that’s not explored here.

EDIT: Sorry, this came across rude, I feel poorly about the tone. I think I'll leave it up as is for posterity's sake but I agree there is a lot we don't know about these conditions.

They have been sequenced pretty thoroughly without identifying an organism. H. pylori and bacteria in biofilms can be detected this way. In the case of asbestos, it seems clear that it is the asbestos particles and not an organism.

As for the tumor microbiome hypothesis, I just find it hard to take a study seriously that suggests that human cancers harbor thermophilic bacteria found in deep sea vents.

I try to support my views by the data we have available, and I think these are currently the most well supported models.

> are we sure inflammation is the root cause and not just a bystander?

The GP stated that it was *a* cause, not *the* cause

True. The question still stands.

Part of the reason cancer is such an interesting field of study in my personal opinion is:

(1) You get a lot of these chicken-or-egg situations where the answer is more like "chicken-AND-egg".

(2) Cancer is almost always the result of a million things going wrong at once... it's a slow unravelling of the bonkers number of safe-guards our cells have to keep them healthy and normal.

Inflammation is a normal part of a healthy, functioning body. It can be caused by anything from scraping your knee to getting a cold. It's useful, and as your comment says, it is an important part to fighting off infections which themselves in rare cases cause cancer. It also plays a pathological role in some diseased like auto-immune disorders, IBS, meningitis, etc...

Inflammation, both the healthy and pathological sort, can help set the stage for tumour to form by contributing to the formation of what's known as a "tumour microenvironment" [0]. Chronic inflammation, often caused by disease, is more likely to keep up this permissive environment than one-off cases, and therefore more likely to result in a tumour

By the way, we understand DNA mutation/damage to work similarly. It happens all the time naturally, and sometimes mutations are fortuitous, but mostly they are ironed out by the cells machinery. Increasing the rate of mutation can overwhelm that machinery and cause tumours to snowball.

So, that's how inflammation can contribute to the initialization of tumours or at least environments that are more permissive of tumours. Tumours, however, also might cause inflammatory response to promote cancer progression through hijacking cell signalling, promoting epithelial-mesenchymal transitions, etc... [1].

We've known inflammation has been linked to cancer since at least 1863 [2], so this is pretty well-trodden territory. The immune system and inflammation is extremely complicated (or at least, I always found it to be), so I'm also not surprised that there are a lot of mysteries lurking.

Finally, to answer your question: I'm sure in some cases inflammation is just bystander. My understanding is that inflammation is not the primary mechanism by which HPV causes cancer, so it is very easy to believe it to be a bystander in that case. H. pylori is a good example of chronic GI inflammation that raises your risk of cancer by way of inflammation. I'm not familiar with the fungal DNA research, so can't comment.

Also disclaimer: It's been a while since I've studied cancer directly, I'm more of a computational biologist these days. Sorry if I made an error here.

[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC6831096/

[1] https://blog.cellsignal.com/hallmarks-of-cancer-tumor-promot...

[2] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

As a software engineer, I'm constantly exposed to system complexity. My experience is that even systems which seem relatively simple from the outside can be extremely complex. Beyond a certain level of complexity, it becomes very difficult to change something without breaking something else. You need to be aware of dependencies when making changes. It appears that the human body is a much more complex system than any software system, with much more complex interdependencies... Given this, it's not surprising at all that it's so difficult to develop solutions to problems like cancer. The whac-a-mole effect must be massive. Seems like every change has countless unintended side effects.

It has built-in error correction but sometimes there are more bits flipped than the correction codes can correct.

Yah that's exactly it. The field of Systems Biology frames things very much in this way https://en.wikipedia.org/wiki/Systems_biology#

A portion of the complexity comes from fixing bugs not at its root-cause. Once you have accumulated many such proximate fixes it becomes quite expensive to fix the bug at the root-cause level. The resident root-cause bug continues to create new problems downstream.

Not much different from biological evolution.

Great point. I chuckle at the fact that 'addressing the root cause' is what naturopaths and 'holistic medicine' practitioners are selling themselves on... Claiming that modern medicine is focused on selling drugs to mask symptoms and doesn't address the root cause... Though their solutions are often even more superficial on average... Besides maybe their approach vitamin deficiencies and supplements.

I don’t want to defend how they report. But for someone who hasn’t been involved in the field, something that’s widely accepted and well-known for a long time can seem “very new” to them.

What is the "80% cause" of chronic inflammation most people should be aware of, so that people may be able to make lifestyle changes to reduce it? What blood tests can I have ordered to measure it?

Excess adipose tissue is a major source of chronic inflammation.

You don't really need blood tests.

Just eat a varied diet, low in ultra processed foods (preferrably none). Limit refined carbs/sugars, excercise regularly, spend time in nature, and don't live in built-up areas with lots of polution. Avoid fragrances, PFAS/PFOA, pftalates and the like.

Chronic stress is a major one.

that sentence starts “in the popular imagination”

So auto-immune diseases ( like arthritis and allergied) and chronic untreated diseases like lyme are the main suspects now?

I don't know about main suspect, but autoimmune disease has been known for a long time to increase your risk of cancer. I have Celiac disease, so an increased risk of stomache, intestinal and bowel cancer.

Honestly, this article is kind of worrying for me, personally. I have many symptoms after two years of treatment with diet alone. Further evidence may eventually show treatment with antibiotics or steroids for people like me may lower more risks then it raises.

As someone with both that sucks

Cancer has many different, simultaneous causes. That's why when people say "x causes cancer" what they mean is x (whatever it is) raises your odds of getting cancer by a measurable degree.

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