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Comment by Gatsky | Hacker News Reader

This has some legal implications. You can now prove fairly conclusively that your lung cancer came from smoking. I wonder if it will lead to a new wave of tobacco litigation.

I think even Fisher would be convinced [1].

[1] https://priceonomics.com/why-the-father-of-modern-statistics...

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Smokers were already and for a long time aware of the risks. They choose to take them. What could they possibly claim? That a product known for causing lung cancer caused lung cancer?

That's a good point, I am not a lawyer so I can't really comment. But perhaps there is a material difference between saying you developed a disease that could have been caused by smoking (as lung cancer occurs in non-smokers), and saying you were definitely harmed by smoking.

Other avenues could be:

- Smoking is also associated with other cancers, such as esophageal cancer and bladder cancer. Generally the warnings don't mention this however. By examining the mutation patterns in an esophageal cancer, you could relate it more conclusively to smoking, and could therefore claim you were not warned about that specific risk.

- Tissue samples from lung cancers diagnosed 20 or 30 years ago are sitting in archival storage. You could sequence the whole genome or exome of these tumours for about $1000 - $2000. Statute of limitations aside, sequencing these tumours could reveal the tobacco signature as a basis for a claim from a time when it was less clear or less public what the risks were.

- Passive smokers could have a case if their cancer shows a tobacco signature.

Lung cancer is caused by smoking 85-90% of the time. Probably more if you add in secondhand smoke. I think it already meets any sort of "preponderance of evidence" sort of bar to just assume anyone with lung cancer got it from smoking.

Citation / reference needed.

I googled it and the same stat on a couple different reputable sites, like that of the American Lung Association and the American Cancer Society.

Suppose that I live in an apartment with a wood stove, second-hand smoke from a room mate, and radon. If I get lung cancer, which one is to blame? How do you know?

I don't see how you can prove particular mutations are tobacco related. DNA can be damaged by viruses, solar radiation, various industrial chemicals, and naturally occurring replication errors. How would you prove this particular mutation was the result of smoking?

I don't see how this research changes anything from a legal perspective. We already knew smoking causes genetic mutations, but we also know people who've never been exposed to tobacco can develop lung cancer.

The aim is to prove that the pattern of mutations in the tumour (which typically contains several hundred mutations in coding regions, more in the whole genome) are caused by smoking.

I think that in all other areas it's been on the manufacturer of products to make them safer over time (cars, children's toys, cosmetics etc.) so shouldn't the tobacco companies be trying to make their product safer?

Not all other areas. Some products are inherently unsafe, and that is precisely what the costumers want. Alcoholic beverages are unsafe, even lethal if you drink too much. They could be made safer by removing the alcohol, but that is not what most people want. The same applies to fast food and sugary drinks: could be made much safer, but people want a certain flavor at a certain price (and most know it's not healthy).

Inhaling the smoke of burning tobacco leaves can cause cancer. I am fairly certain nobody has as strong of an incentive to create cancer-free tobacco as tobacco companies do. That does not mean it is possible, right?

Alcoholic beverages are not unsafe if consumed in the recommended amounts (which are fairly reasonable. 2 drinks on average, with a 3 drink max).

What's the safe, reasonable, recommended smoking amount?

I would recommend puff, puff, pass. Otherwise you risk the chance of a bogart.

Zero (cigarettes are highly addictive).

My point is that reality limits how much safer you could make a product. Would it be nice for cigarette or alcoholic beverages to be safer? Yes. Is it possible? Apparently not.

Either tobacco becomes a controlled substance (I am deeply opposed to this given the catastrophic social consequences of prohibition in general), or adults behave like adults, understand the risks, decide for themselves and accept the consequences. Maybe it's because I'm European, but anything else sounds like insanity to me.

By the way, I am not being judgemental in any way. I am an ex-smoker and I drink socially. If people want to smoke (without polluting the environment of others who don't) it's their right, and I completely understand. I used to love it too.

> Either tobacco becomes a controlled substance

What on earth are you talking about? Tobacco is already a controlled substance in more ways than nearly anything that you can buy at a store (including guns).

I meant prohibited, of course. I think that is fairly obvious from the context of my post. Sorry for the lack of rigor.

Where I live it is almost impossible to buy a gun. On the other hand, I can go downstairs and buy a pack of cigarettes with the same ease that I could buy bubble gum. No questions asked, no ID needed, no records.

  "Some products are inherently unsafe, and that is precisely what the costumers want."

Radioactive material in tobacco might be mutually exclusive from nicotine and MAOI content. My layperson guess is getting rid of the radioactivity would require prohibitively expensive hydroponic growing. It's the drug part that consumers want, and I'm pretty sure if given the knowledge and option they'd go for non-radioactive cigarettes.

Swedish snus is made to minimize tobacco-specific nitrosamines (TSNAs), but seems to not address Polonium-210 on account of the radioactive stuff being "comparable to that from the natural background radiation sources or dental x-rays": https://harmreductionjournal.biomedcentral.com/articles/10.1...

That excuse doesn't seem to hold up to scrutiny. Who really wants to have 10-20 chest x-rays done per day? Are "dental" x-rays really as weak as "background" radiation?

Alcohol seems to be in a similar position - see the popularity of nice wine and beer over e.g. guzzling cheap spirits.

I think people want health AND pleasure, and are willing to do their own hedonic calculus.

It is possible to make them less carcinogenic. Carcinogens come from fertilizers and pesticides (which could be controlled/replaced), from the curing process (which could be replaced with anaerobic curing), and from additives (which could not be added). So a lot could be removed, but there is still inherent bad stuff in breathing smoke. That's enough to cause blowback from people who are afraid that advertising "safer cigarettes" would encourage more people to smoke. Lengthy expensive IP/patent lawsuits have also delayed development. And of course there's the issue of whether customers like it, whether it's profitable, and how much it cannibalizes the tobacco company's other business.

Possible to improve? Yes, perhaps significantly. Economically and politically feasible? Maybe not so much.

They could easily claim that a product which would otherwise would not have these risks was made into a risky product by the use of certain carcinogens present in the pesticides. The choice of pesticide is made by the tobacco company, so it is their actions that introduce the carcinogen into the product.

Seems pretty standard to me, and I would have to guess that this is the kind of lawsuit that you would probably support if the product in question was, say, red meat instead of tobacco.

I'm not sure that this could prove that. I believe that the mutation rate for non-smokers that develop lung cancer should be elevated as well. Perhaps there is a statistical difference, but it might not be easy to prove with certainty.

The tobacco signature goes beyond elevated rate, it has a sequence specific pattern (see http://cancer.sanger.ac.uk/cosmic/signatures).

Very interesting, does look promising indeed. However, currently it still seems unclear that they have enough data to say with certainty that these "signatures" are unique or complete.

From your source:

> With more cancer genome sequences and the additional statistical power this will bring, new signatures may be found, the profiles of current signatures may be further refined, signatures may split into component signatures and signatures may be found in cancer types in which they are currently not detected.

These signatures will never be unique or complete. Remind you that this is biology where there is not the TRUTH to be found. At some point you can always subdivide one phenomenon in to two cases. These signatures are generated from non-negative matrix factorization which generates signature vectors more or less stable depending on the amount of input datasets and the number of signatures you want to obtain. And at some point you are limited by the amount of money you have for these dataset (still more than $1000 per patient) and how many patients exist in the end (there may be correlations we will never get to know because the search space is much bigger than the 7 billion people we are can provide in correlations.

You leave out the fact that there is a known carcinogenic mechanism for smoking, and this corresponds to the signature derived by NMF. In vitro studies in controlled systems exposed to smoking carcinogens also reproduce this signature. In addition to the NMF signature, there are other features like transcriptional strand bias, and dinucleotide substitutions. This is a bit more than an association.

Would be interesting to see how many mutations people have who live in houses with a high level of radon.

Hitting yourself repeatedly over the head with a hammer can give you a headache. Not sure DeWalt are worried from a litigious point of view. I doubt there is a smoker alive today who can reasonably claim to have been unaware of the risks when they started.

Anal point - why the apostrophe? Should it be "Smoking becauses hundreds..."?

There is literally a 69 year old woman in the article who claims just that:

> "Had I known as a teenager that smoking caused mutations which would stay with me for life then I would never had started"

It agree with you that it's a little silly, especially for young people, but it wasn't that long ago they started forcing cancer warnings on tobacco.

I'm an ex-smoker and I had the same thought as I read the article: I wish I'd known this.

But really, I know it wouldn't have made a difference. From an early age I was taught at school that smoking would kill me and I started anyway. The idea that detailed knowledge of one particular cause of death would have made a difference is laughable. It's just a way of deflecting blame from one's own responsibility.

I dunno, there's a fun argument to be had about informed consent.

It's fair to say that everyone know smoking is bad by now, but does everyone possess a correct and complete enough understanding of how and why to meaningfully consent to the risks? If you understand that smoking can cause cancer, but not that it can cause cancer even years after you stop smoking, is that good enough? If you think you can go on a cleanse and purge the toxins from your body, are you really competent to consent to the long-term risks? We don't let minors do nearly anything, from sex to signing contracts to receiving medical treatment, because we do not believe they are mature enough to properly weigh the consequences. If a minor decides to begin smoking, are they able to meaningfully consent to the risks, even if they have been adequately explained?

All medical interventions are weighing hopefully large benefits against hopefully small side effects, but even terrible side effects can be acceptable if the benefits are large enough and people receiving the treatments have been adequately informed and can meaningfully consent.

Not sure where you live but in my country we already don't let minors smoke.

In most parts you can legally have sex before you can legally smoke.

In my country it is illegal for minors to smoke, and a majority of smokers start smoking as minors.

Well sure but I'm just pointing out that the analogy isn't great. There are already plenty of things minors can't legally do and we don't try to ban them for everyone.

It's not a question of illegal or not, it's a question of whether smokers are able consent to the risks of smoking, and therefore whether the companies are absolved of damages.

Your argument was that minors cannot meaningfully consent to the risks. But smoking is already illegal for minors.

How can a company be held liable for people who choose to use their product illegally? This doesn't make sense.

(It's different of course if they are directly encouraging children to smoke. In that case, they should have the book thrown at them.)

This is just an old woman being dishonest with herself. The US was the 1st to put warnings on tobacco packaging in 1966. This was about the time this woman started smoking. Is it really believable that an additional scientific data point about the harm would've swayed her decision? Especially one she wouldn't have even understood at the time? It's always been abundantly clear that inhaling smoke into your lungs is not a good idea - the scientific details aren't really necessary in making the decision not to smoke. What was necessary was a shift in the culture and advances in general healthcare which made the trade-offs worth the delayed gratification

There are plenty of people alive today who were unaware of the risks because until about the mid-80s the cigarette companies could actively deny them. You can only argue ignorance from when the mandatory product warnings were introduced.

In the US warnings were introduced in 1966.

It's not an apostrophe, it's a single quote. The article title is:

> Smoking 'causes hundreds of DNA changes'

I'm guessing HN trimmed the closing quote to change it to:

> Smoking 'causes hundreds of DNA changes

It's now been changed to:

> Smoking “causes hundreds of DNA changes”

Those are weird quotes too, not the normal ". There are lots of different quote characters. :)

Pedants will probably like this magazine: http://media-cache-ak0.pinimg.com/736x/df/b7/74/dfb7741e5e84...

Is there anyone marketing cigaretts able to claim they're unaware? Aren't those also adults?

I smoke (trying to quit) and I don't think cigarette manufacturers are doing anything immoral. I enjoy smoking! Why else would I have ever tried it when I knew all the risks?

Nobody is getting tricked, here. People are selling a product that other people want.

Have you read "the easy way to stop smoking"? He makes a great point about the claim that smokers don't actually enjoy it. It's addiction, thinking you enjoy it is a mechanism of avoiding the guilt of the addiction. Or something like that, his argument was much more convincing.

That's akin to saying "you don't actually enjoy eating food, you're just hungry". Addiction and enjoyment are not mutually exclusive.

The obvious difference being: that is not the intended use for a hammer.

>"I think even Fisher would be convinced [1]."

I doubt it, he would probably say no progress has been made at all:

"Many would still fell, as I did about five years ago, that a good prima facie case had been made for further investigation. None think that the matter is already settled. The further investigation seems, however, to have degenerated into the making of more confident exclamations, with the studied avoidance of the discussion of those alternative explanations of the facts which still await exclusion.

[...]

the B.B.C. gave me the opportunity of putting forward examples of the two classes of alternative theories which any statistical association, observed without the predictions of a definite experiment, allows—namely, (1) that the supposed effect is really the cause, or in this case that incipient cancer, or a pre-cancerous condition with chronic inflammation, is a factor in inducing the smoking of cigarettes, or (2) that cigarette smoking and lung cancer, though not mutually causative, are both influenced by a common cause, in this case the individual genotype." https://www.york.ac.uk/depts/maths/histstat/fisher269.pdf

The current paper: "Although we cannot exclude roles for covariate behaviors of smokers or differences in the biology of cancers arising in smokers compared with nonsmokers, smoking itself is most plausibly the cause of these differences." http://dx.doi.org/10.1126/science.aag0299

Proof of smoking causing cancer was established a long time ago entirely without DNA evidence. I don't think convincing Fisher is/was important: there are several cases where he used his big brain to rationalize things that we clearly know are false.

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