Smoking “causes hundreds of DNA changes”

[qb45]

Trivia:

Polonium-210 in tobacco contributes to many of the cases of lung cancer worldwide. Most of this polonium is derived from lead-210 deposited on tobacco leaves from the atmosphere; the lead-210 is a product of radon-222 gas, much of which appears to originate from the decay of radium-226 from fertilizers applied to the tobacco soils.

https://en.wikipedia.org/wiki/Polonium#Tobacco

[zymhan]

Would organic tobacco avoid the issue of Polonium then?

[amelius]

So wouldn't other crops have this problem? I.e., the stuff we eat every day?

[ambicapter]

Why is there radium in the fertilizer?

[agumonkey]

And we only hear about partial combustion harmful byproducts..

[Gatsky]

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...

[TelmoMenezes]

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?

[CoryG89]

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.

[nthcolumn]

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..."?

[nonbel]

>"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

[dekhn]

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.

[nonbel]

>'Prof Stratton said in these organs smoking seemed to be accelerating a natural mutational process, but how it did this was "mysterious and complex".'

Wow, just wow. This is standard Armitage & Doll model that has been taught since the 1950s.

Every time a cell divides there is some chance of a genetic error occurring. The more generations away from the zygote a cell is, the more genetic errors it will have accumulated.

Activities that damage tissue, etc and necessitate cell division to replenish the cells will contain cells with more errors.

Now that is a vague sketch, but many people have implemented mathematical/computational models based on that idea, beginning with Armitage and Doll in 1954. Unless he is going to reject the model that has been driving cancer research for half a century (which should be noted in the interview), there really is no mystery at all.

[scottishfiction]

It would be unfair to assume Prof Stratton is unaware of this model, rather than simply tailoring a technical finding to a non-technical audience.

[7Z7]

You mistake the doctor's statement to the BBC with what the BBC chose to extract from it, to publish in their single sentence precis.

[rubicon33]

'Every time a cell divides there is some chance of a genetic error occurring.'

Why is that cell allowed to exist then? Isn't there a quality control mechanism or something, that can detect an error occurred and delete the cell?

[schmidty]

Are they truly "errors" or deviations which could be good or bad?

[nonbel]

Unless I am misunderstanding something, their figure 3 seems to be plotting effect size vs p-value... So all it would be showing is that they had more data from lung adenocarcinomas (ie sample size is larger for that cancer type). It isn't 100% clear to me if they shared the data used for that figure, but here are the frequencies each cancer type appeared in table S1:

  Acute myeloid leukaemia (AML)                       Bladder 
                            202                           399 
                         Cervix             Colorectal cancer 
                            168                           559 
      Esophageal Adenocarcinoma           Esophageal Squamous 
                            242                           292 
                 Gastric cancer                        Kidney 
                            472                           257 
                         Larynx                         Liver 
                            123                           392 
                     Lung Adeno                 Lung Squamous 
                            678                           175 
                    Oral cavity                Ovarian cancer 
                            363                           458 
                       Pancreas                       Pharynx 
                            239                            76 
         Small Cell Lung Cancer 
                            148 

It is essentially just figure 1 from here: https://arxiv.org/abs/1311.0081

[nonbel]

Looking more I see:

"Comparison of overall methylation between smokers and non-smokers was performed for all tobacco-associated cancer types for which there were available data from Illumina Infinium HumanMethylation450 BeadChip array, where each array contains 473,864 autosomal CpG probes. The examined data were downloaded from the original data source (Table S1)

[...]

distributions were subsequently compared between smokers and non-smokers using a two-sample Student’s t-test. Results were considered significant for Bonferroni threshold of 10-7."

So it is not like figure one from that Lew paper, because their effect size is not normalized to the inter-individual variance. This is a point in their favor.

However, the sample sizes do match up to those found in table S1 (which I posted above). From the data provided, we cannot tell whether that difference in p-values is solely due to sample size or not. They need to tell us the variance for each CpG/tissue combo as well.

[teamonkey]

Does anyone know the baseline rate for mutations for a non-smoker?

Edit: Corrected autocorrect

[pazimzadeh]

"In the absence of mutagens, an average gene will mutate about once in a million generations. ~10^16 cell divisions occur in a typical life span so somewhere in cells that are part of you each of your genes has mutated 10^10 times (hence cancer). Only mutations in the germ line can be passed on to the next generation. You have about 50 mutations that your parents dont have (mutations that happened in the egg or sperm that made you up)-each of your parents in turn have passed on ~50 mutants that their parents dont have."

Source: an email from my undergrad genetics professor

[CppCoder]

I read the original study and yes, they did compare it to lifelong non-smokers. However, as far as I saw they only compared people with cancer. And the numbers were usually increased for smokers and the smokers usually ended up with more of a certain kind of cancer.

[jjn2009]

If you meant nonsmoker then you asked the most relevant metric in my opinion.

[trustfundbaby]

I wonder if drinking does the same?

[CoryG89]

I wonder if there is just about anything (other than water) that you can put in your body that wouldn't have some effect on the mutation rate of some particular cells in your body.

[forgotpwagain]

I would expect so.

Alcohol can cause inflammation, triggering various parts of the immune system to kick in. This could result in the release of free radicals from these immune cells, which promotes DNA mutations.

[zimbatm]

So how much more is it compared to a non-smoker? I understand the idea of shock factor but everyone gets mutations, it would be nice to get a baseline.

[flukus]

So us smokers are more highly evolved? /s

[labster]

Evolution doesn't have a high or low state, or a linear progression. It's a natural process that is random and responsive to environment changes, not progressing towards an ideal.

[WheelsAtLarge]

I suspect there are multiple reasons for the DNA changes. One that comes to mind is the number of times the lungs have to repair themselves due to the tar and other contaminants. The hot smoke might even contribute to the tissue damage. Cancer is uncontrollable cell growth. The cell/body's ability to control a certain type of cell division has been lost.

So, my thinking is, in the same way that you lose quality as you make a copy of a copy in a copy machine the same happens to the cell's DNA. The more a cell has to divide the less the DNA can remain without errors. DNA can tolerate a number of errors but it can eventually lead to cancer. My guess is that not one issues causes the DNA changes but and array of them given the number of substances a cigarette has.

[melling]

What about the study that said 15 years after you quit smoking, your chances of dying are the same?

https://www.yahoo.com/beauty/are-former-smokers-safe-after-1...

[kawera]

I wonder if there were studies that analyzed the effect of smoking non-industrialized cigarettes. I smoke 2-4 cigarettes per day and make my own cigarettes from tobacco leaves that I dry/shred myself. The leaves in turn come from a few organically grown plants.

[nabla9]

The quality of tobacco does not matter. Homegrown can be even more harmful.

The main reason tobacco is so dangerous is because you are inhaling smoke and carcinogens that are created in the burning. Burning organic or non-organic makes no difference. You are like firefighter in a burning house without a mask when you inhale.

http://www.livescience.com/7914-warning-homegrown-tobacco-de...

[mountaineer22]

Also, you are controlling your own dose (by how big you roll and pack your cigarette), no?

I feel with industrialized cigarettes, most users feel obligated to consume it completely.

My father-in-law would smoke a portion of the cigarette, put it out, and resume later.

[fithisux]

So, why do they sell cigarettes?

[6502nerdface]

People vary in what gives them pleasure and in their valuation of the time/pleasure trade-off. Cigarettes are a tool for some people to move pleasure from the future to the present (i.e., shorter life/less future pleasure in exchange for more pleasure now); they adress intertemporal pleasure-flow needs for some, much as loans address intertemporal cashflow.

[mobiuscog]

Money

[nom]

Because people like to smoke. It's more than pleasurable, but only iff you are able to either ignore or accept the consequences (or you are simply not aware of them).

[DominikR]

It is not your business to decide what other people should do with their lives.

Go live in North Korea or Venezuela if you desire having a dear leader who tells you what you should do with your life and leave us alone.

[umanwizard]

Why do they sell richly marbled steak when we know it causes high cholesterol?

[Shivetya]

while there are some studies that do not put marijuana smoking as high on the danger list [1] I am really curious that as legalization increases what will we see in the future. Then of course there is the loosely regulated area of vaping and who knows what is in some of those fluids. For the most part I am quite sure they have to be safer than smoking but I would love some hard regulation.

2005 study on marijuana smoke > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1277837/

[roflchoppa]

Yeah my buddy has been thinking about moving over to just vaporizing marijuana, opposed to smoking it in papers. Might as well remove what you can?

[ddorian43]

You can always go for vaporizers. Are vaporizers actually ever used on tobaco? (i think they're sold "for tobaco use only" like bongs?)

[venamresm__]

That reminds me of the British information video: https://www.youtube.com/watch?v=sWfOLN9Z1yw

[sireat]

Is there anything you can do to help your odds of not dying from lung cancer once you have stopped smoking?

Any yearly tests to perform?

I was a 10cigs a day smoker for 15 years(quit some years ago) and it really weights heavy on my mind that there is nothing I can do about my past mistakes.

[sidcool]

How addictive is tobacco/smoking as compared to Opiates/Heroin?

[delegate]

I've once read somewhere that they polled heroin addicts, asking them what they'd rather do first time they wake up in the morning - shoot heroin or smoke a cigarette.

Of course the vast majority said they'd smoke a cigarette.

I've never been a heroin addict, but I've been a tobacco smoker for many years and I can confirm that smoking a cig was definitely the most important thing I had to do in the morning.

Also if I had to spend my last money on food or a pack of cigarettes, obviously and without further consideration, I would choose the cigarettes.

So yeah, pretty addictive.

[drusepth]

So, could we detect what properties of smoking map to which DNA changes, and design a cigarette that maximizes net-positive DNA changes while minimizing harmful/negative ones?

[tonyplee]

Next Ad for Tobacco: If you smoke hard enough, you might become X-man.

[fithisux]

Smoking causes COPD too.

[pizza]

Anything similar about vaping/e-cigs?