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England's department of health has launched a new, very graphic anti-smoking TV ad (see the BBC STORY). Aside from the graphic imagery it makes the specific claim that a smoker will suffer one mutation for every 15 cigarettes smoked.

Is this claim credible? And, perhaps more importantly, is it significant given the background level of mutagenic chemicals and radiation we are exposed to?

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It might be mentioned that the mutations being talked about are mutations to individual DNA molecules that would lead to cancerous growth. They are not mutations to the organism that would track through to a new generation. –  Tim Quinn Dec 28 '12 at 22:35
    
@TimQuinn If I read the paper correctly, they're actually mutations that are apparent within the cancerous cell line, not mutations taken from pre-cancerous tissue. –  Larry OBrien Dec 29 '12 at 0:35
    
I guess what I suspect is that Matt thinks that cigarette smokers are more likely to have deformed children. They are not talking about mutations to the organism that would be inherited by an off spring but mutations to individual DNA molecules that will result in localized cancerous growth within the organism. This is only meant as a clarification to the questioner about what is going on. I might be totally wrong, but it would explain why Matt thinks it is extraordinary that so many mutations happen. –  Tim Quinn Dec 29 '12 at 10:23
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@TimQuinn To clarify: I was not assuming there would be germ-line mutations; I assumed the mutations would be in lung or airway cells. I asked the question because I wanted to see whether there was a clear scientific justification for the number in context. –  matt_black Dec 29 '12 at 12:36
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I see a new ad campaign: "Go ahead, kids! Fourteen won't kill you!" –  Larry OBrien Dec 29 '12 at 18:37
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4 Answers 4

Yes, the number is derived from a study published in Nature:

If the majority of mutations derive from the mélange of mutagens present in tobacco smoke, the clone of cells that ultimately becomes cancerous would acquire, over its lifetime, an average of one mutation for every 15 cigarettes smoked. If this is the case in a localised cluster of cells, then the number of mutations acquired across the whole bronchial tree from even one cigarette must be substantial. The data presented here demonstrate the power of whole genome sequencing to disentangle the many complex mutational signatures found in cancers induced by tobacco smoke.

Pleasance et al., 2010

To my layman eyes, it appears that the finding is highly significant, but not so much because of the magnitude of mutations, but because there are specific cancer-related signature mutations:

Even in this single lung cancer genome, we can identify several distinctive point mutation patterns, reflecting the cocktail of carcinogens present in cigarette smoke, as well as signatures of the partially successful attempts of the cell's surveillance machinery to repair DNA damage.

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this is a good answer. A great answer would also explain how the cell-line that was sequences was derived and provide some of the missing estimates of background mutation rates in normal cells. –  matt_black Dec 31 '12 at 14:57
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In 2010 the Wellcome Trust published One mutation per 15 cigarettes: genome maps reveal how cancer develops

"These are the two main cancers in the developed world for which we know the primary exposure," said Professor Mike Stratton, from the Cancer Genome Project at the Sanger Institute. "For lung cancer, it is cigarette smoke and for malignant melanoma it is exposure to sunlight. With these genome sequences, we have been able to explore deep into the past of each tumour, uncovering with remarkable clarity the imprints of these environmental mutagens on DNA, which occurred years before the tumour became apparent.

The same source was given in a 2009 article in The Daily Telegraph

They studied a lung-cancer victim who had built up about 23,000 DNA mutations in his lung cells that were linked with exposure to the toxins found in cigarette smoke and had accumulated over his lifetime.

(The newspaper doesn't state whether this is one example of a larger sample)

The study was also reported in 2009 by Nature and Medical News Today


I believe the above to be supportive of the credibility and significance (re causes) of the claim.


Update:

I haven't found information on rates of mutations attributable to other causes of cancer but many credible organisations say that smoking accounts for around 90% of lung cancers in the UK.

Cancer Research UK, BBC, MacMillan, BUPA.

Here's an infographic from Cancer Research UK - it has a lot of information.

Cancer causes

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+1 good answer. But I'm still looking for the broader context about background rates as well. Otherwise I have no basis to judge the significance. –  matt_black Dec 28 '12 at 18:15
    
The paper is available ncbi.nlm.nih.gov/pmc/articles/PMC2880489 –  Larry OBrien Dec 28 '12 at 20:13
    
And I hate the infographic it is a poor way to visualize that data whether or not the stats are correct (which is debatable for some, though not for tobacco.) –  matt_black Dec 29 '12 at 0:53
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Interesting to note - it is not even known whether the patient from which these cells were originally derived was in fact a smoker!! We don't even know if he smoked 1 cigarette, 15 cigarettes or 150,000 cigarettes.

From the original Nature paper...

NCI-H209 is an immortal cell line derived from a bone marrow metastasis of a 55 year old male with SCLC, taken before chemotherapy. The smoking history of the patient is not recorded. However, the specimen showed histologically typical small cells with classic neuroendocrine features: >97% of such tumours are associated with tobacco-smoking.

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Why the down votes? I thought bob was adding a relevant piece of information from the key paper. –  matt_black Dec 30 '12 at 13:40
    
I didn't downvote, but the next line in the quoted text states why that piece of information isn't necessary relevant. In short, is this a good answer to the original question? –  Zano Dec 30 '12 at 16:53
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Baser on this study I believe the mutation rate from smoke is likely to be much higher. This study found 1 mutation per 15 cigs smoked in the cancer cell line. Note that this is just the mutations induced in the cell that eventually became cancerous. Since mutations are induced randomly in all exposed cells, the other cells in the lung will likely have acquired their own set of mutations in parallel with the one that became cancerous. It's just that the cancerous one was the first to get a complete set of mutations required for cancer. So the actual number of mutations in the lungs might well be millions or even billions per 15 cigarettes.

This is not surprising at all. Just one drag contains nanogram amounts of benzoapyrene and NNK and other nitrosamines which react readily with DNA and induced mutations. In fact it is among the most mutagenic substances ever discovered. One nano gram may not sound like a lot but it is still hundreds of billions of molecules of these molecules randomly entering your lungs with every drag. 9/10th of the inhaled tar is absorbed and will have plenty of time to penetrate a cell and induce mutations.

Addition jan 3rd: I realize that you didn't like my post very much. But my point is valid and I haven't seen it mentioned anywhere else including in the study or in other discussions (otherwise I would happily post a referene... problem is, such a reference doesnt exist). Namely that it is wrong to say that 15 cigs creates 1 mutation. In truth the number is much higher since all cells of the lung accumulate the smoke induced mutations but their study counts only the ones in the cancer cell line, thereby grossly underestimating the true number of mutations per cigarette. The study has other flaws as others pointed out.

So now I said it. My point stands whether you like it or not :)

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This post does not cite any references or sources. Please help improve this post by adding citations to reliable sources. Unsourced material may be challenged and removed.

    
Welcome to Skeptics. Please provide some references to support your claims. From just two sentences, you need to explain how you know benzoapyrene is in tobacco smoke, at the nanogram level, and that it reacts with DNA and that it is amongst the most mutagenic substances ever found. Then the same for NNK and other nitrosamines. Whether we "like it or not" is irrelevant - your point doesn't stand until you show it is true with references. –  Oddthinking Jan 3 '13 at 14:38
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