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Smoking “causes hundreds of DNA changes”

bbc.com

251–259 of 259 posts

Re: Smoking “causes hundreds of DNA changes”

#251

Earlier quoted context omitted.

Tell you or order you? I wrote "nobody gets the right to decide for someone else".

Well, here's how I see it. I understand what you are trying to say, it is not your (or anyone's) business to decide what other people should do with their lives, specially if it doesn't affect others. And, so no one (or governments) should intervene and regulate/ban sale of cigarettes. Would you feel absolutely the same way about all banned substances? If not, well you should agree that different people would draw th…

> Would you feel absolutely the same way about all banned substances?

Yes, absolutely. If people want to ruin their lives it's not my responsibility to keep them from doing it. It's their own decision and all consequences are their own problem.

Re: Smoking “causes hundreds of DNA changes”

#252
post #237

Earlier quoted context omitted.

OP's comment misinterprets a quote; it's great to bring up that model, but it's ludicrous to think that Mike Stratton does not know it in far greater detail than nonbel, as I would place Stratton as the world's authority on cancer mutations. He was the senior author on the authoritative survey of cancer mutational processes: http://www.nature.com/nature/journal/v500/n7463/full/nature1... In addition, nonbel's snarkin…

Lets gather info from the paper and see if what they say makes sense. In discussing figure 1, they seem to know this data needs to be normalized to number of cell divisions: >"The prevalence of somatic mutations was highly variable between and within cancer classes, ranging from about 0.001 per megabase (Mb) to more than 400 per Mb (Fig. 1). Certain childhood cancers carried fewest mutations whereas cancers related t…

This isn't like a long crackpot screed. It is a couple paragraphs... Why downvotes without explanation? Where did I go wrong (I see some typos at the bottom "78 generations separated" should be "7000", but that shouldn't be a huge deal)?

Re: Smoking “causes hundreds of DNA changes”

#253
post #33

Earlier quoted context omitted.

The premise is highly unsound. This study is talking about somatic mutations, which can only be harmful to an organism. Why? Because they can be beneficial to an individual selfish somatic cell, which is what we can cancer. In other words, when a somatic mutation is succesful, it spreads and becomes cancer. And of it doesn't spread, it can't have a serious impact on the phenotype of an entire organism. So, the mutati…

"Can only be harmful" is pretty strong. You could have a set of mutations in a T-Cell for example that makes it super good at killing all forms of cancer.

I'm still skeptical- I doubt a single T-cell can have anything but a ever so slight statistical inpact on the phenotype of an entire organism, and there is no selective process to keep that mutation around, so it cannot last long in the body, either.

Re: Smoking “causes hundreds of DNA changes”

#254

Earlier quoted context omitted.

Well, here's how I see it. I understand what you are trying to say, it is not your (or anyone's) business to decide what other people should do with their lives, specially if it doesn't affect others. And, so no one (or governments) should intervene and regulate/ban sale of cigarettes. Would you feel absolutely the same way about all banned substances? If not, well you should agree that different people would draw th…

> Would you feel absolutely the same way about all banned substances? Yes, absolutely. If people want to ruin their lives it's not my responsibility to keep them from doing it. It's their own decision and all consequences are their own problem.

This is an absolutist view, while it is quite a compelling argument for certain extreme cases, I am afraid the world is never that black and white. Since we are talking about regulating/banning substances, let me try to point it out with a relevant example. While it might seem fair to say that if someone wants to ruin their own life by substance abuse, why should it be my (or the government's) responsibility to keep them from doing it. But, consider this, one of the growing problems right now in the US is opioid dependence and addiction. In these cases, these opioids are medication that is prescribed by doctors to treat acute pain. But, along with providing pain relief, this medication can cause opioid dependence and addiction over time. A sizable population of regular people who were just seeking treatment for their illness, unfortunately ended up with opioid addiction. This could just as easily happen to any of us or our loved ones. I can't speak for you but I would definitely want the government to step in, fund relevant research to study the problem, based on that perhaps regulate (or ban, if necessary) the availability and/or prescription of such medication because though it provides pain relief, it has unintended consequences that ruin lives of unsuspecting people.

Government regulation isn't necessarily always bad. There is no absolutist one-size-fits-all solution for all problems. Would I like the government to tell me what I can and cannot do, absolutely not. I would protest with you if I think government is overreaching. But, would I concede that there are certain issues (which might not affect me, but might affect lot of others) where the government has to intervene, of course, yes.

Re: Smoking “causes hundreds of DNA changes”

#255
post #233

Earlier quoted context omitted.

No need. Nicotine is absorbed by the soft tissues of the mouth. Inhaling prevents you from "correctly" smoking a pipe. Take a look at this (formatting mine): "The Breath Smoking Technique It requires a relaxed setting, preferably sedentary and a very slow and calm breathing pattern. The pipe bit is held to the lips continuously and all breathing is through the nose. Every 2nd or 3rd slow breath through the nose, a ti…

I know all this. I smoke cigars the right way. I also know cigarette smokers that cannot help themselves when smoking cigars. They inhale.

There is no "right" way to smoke a cigar. It's your cigar. Smoke it however the fuck you want to smoke it.

Re: Smoking “causes hundreds of DNA changes”

#256

So, why do they sell cigarettes?

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.

I absolutely loved this explanation.

Re: Smoking “causes hundreds of DNA changes”

#257
post #167

Earlier quoted context omitted.

Nicotine gum? The danger is in the smoking, not the addictive substance.

> The danger is in the smoking, not the addictive substance. Actually, that's incorrect. Nicotine acts as a stimulant and constricts blood vessels, which causes all kinds of serious circulatory problems in the long term - high blood pressure, heart attacks, strokes and so on. Unfortunately there's no easy way around nicotine, you just have to stop ingesting it. The gum/patch can alleviate the withdrawal symptoms, but…

Ehh, sez you..

http://circ.ahajournals.org/content/130/16/1418

"There are some studies of prolonged nicotine replacement therapies (NRT) in smokers who have quit smoking. In these studies, no adverse effects have been found when nicotine medication was administered for months to several years. Other studies indicate that patients with known cardiovascular disease tolerate NRT well for periods up to 12 weeks. "

By far, the danger is in the smoking, not the nicotine in your bloodstream.

The Gallup survey

http://www.gallup.com/poll/163763/smokers-quit-tried-multipl...

allowed an open-ended response, so someone "might have decided to quit" or quit because "it was time" but also used an NRT to help them through the cravings and not have mentioned that to the interviewer.

Re: Smoking “causes hundreds of DNA changes”

#258
post #252
post #237

Earlier quoted context omitted.

Lets gather info from the paper and see if what they say makes sense. In discussing figure 1, they seem to know this data needs to be normalized to number of cell divisions: >"The prevalence of somatic mutations was highly variable between and within cancer classes, ranging from about 0.001 per megabase (Mb) to more than 400 per Mb (Fig. 1). Certain childhood cancers carried fewest mutations whereas cancers related t…

This isn't like a long crackpot screed. It is a couple paragraphs... Why downvotes without explanation? Where did I go wrong (I see some typos at the bottom "78 generations separated" should be "7000", but that shouldn't be a huge deal)?

I didn't downvote, but it definitely does come across as a crackpot screed. You are discounting data in favor of an overly simplistic statistical model. You also greatly misinterpret a key point in the quote: they're not saying all mutations accumulate at a constant rate, but only a few signatures appear to. In fact, the very next sentence of that quote is:

>The absence of consistent correlation of all other signatures with age suggests that mutations associated with these have been generated at different rates in different people, possibly as a consequence of differing carcinogen exposures or after neoplastic change has been initiated.

This is a classic crackpot technique: selectively quote just the parts that you want them to say, twist it a bit further to your needs, then proceed with an overly simplistic, but supposedly impressive analysis. I don't know or really think that you are a crackpot, but the quoting behavior is quite telling.

Getting back to your original comment, you accuse the authors of this paper:

http://science.sciencemag.org/content/354/6312/618.full

of not knowing what they're talking about. But in reality, you have already mistaken the type of process that's being talked about. Stratton is talking about a biological and chemical process. You're talking about a "random" process from statistics. An old theory, that uses simplifying assumptions that do not apply with this data.

And finally, the most obvious reason that the Armitage Doll process is not the best explanation is that AD were looking at the process of carcinogenesis. This paper is looking at the various processes of mutations that happen because of a carcinogen. These are different things, especially since mutational processes accelerate after carcinogenesis. I believe the paragraphs that you would find most interesting from the paper are here:

>Signature 5 is found in all cancer types, including those unrelated to tobacco smoking, and in most cancer samples. It is “clocklike” in that the number of mutations attributable to this signature correlates with age at the time of diagnosis in many cancer types (17). Signature 5, together with signature 1, is thought to contribute to mutation accumulation in most normal somatic cells and in the germline (17, 23). The mechanisms underlying signature 5 are not well understood, although an enrichment of signature 5 mutations was found in bladder cancers harboring inactivating mutations in ERCC2, which encodes a component of NER (24).

>Signature 5 (or a similar signature that is difficult to differentiate from signature 5 because of the relatively flat profiles of these signatures) was increased by a factor of 1.3 to 5.1 (q Armitage Doll relates at most tangentially to what is being reported by these scientists.

Re: Smoking “causes hundreds of DNA changes”

#259
post #252

Earlier quoted context omitted.

This isn't like a long crackpot screed. It is a couple paragraphs... Why downvotes without explanation? Where did I go wrong (I see some typos at the bottom "78 generations separated" should be "7000", but that shouldn't be a huge deal)?

I didn't downvote, but it definitely does come across as a crackpot screed. You are discounting data in favor of an overly simplistic statistical model. You also greatly misinterpret a key point in the quote: they're not saying all mutations accumulate at a constant rate, but only a few signatures appear to. In fact, the very next sentence of that quote is: >The absence of consistent correlation of all other signatur…

Thanks for responding, I hope to get back to you in more depth. But first of all:

>"An old theory, that uses simplifying assumptions that do not apply with this data."

Yes, get rid of one simplifying assumption that was originally introduced for computational reasons and is totally unnecessary today (low mutation rate), and you can see it is impossible for that theory fit the age-specific incidence data using accepted mutation rates + division rates.

Something is wrong, yet in the supplement of the Alexandrov et al (2016) paper, which has the same first and last authors as Alexandrov et al (2013) paper you cited, they use this model without comment on that issue.

Also, in the 2013 paper, Armitage-Doll is not mentioned but it is clear to anyone familiar with that model that it is guiding their interpretation of the results.

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