Chemicals and cancer, signal and noise

By Razib Khan | July 2, 2013 7:07 pm

Pancreatic cancer tissue

George Johnson is out with a new book, The Cancer Chronicles: Unlocking Medicine’s Deepest Mystery, and is also now at the center of a host of controversies due to some of his conclusions after years of research and writing. You can keep track of the volleys back and forth at his blog, Fire in the Mind. But I want to you pay close attention in particular to a new piece in Discover (print edition), Prehistoric Times: The idea that cancer is a modern disease is a common misconception — one that the fossil record reveals to be untrue. Here’s the big bold assertion: correcting for the greater longevity of modern people the rate of cancer is no higher today than it was in the human past. This is a shocking claim, and bound to cause controversy.

Though I am not able to judge the validity of this assertion in the specifics, it is not implausible on the face of it. Many of the claims for correlations between particular chemicals or environmental inputs and disease later on in life are subject to the problem of numerous confounds. It’s hard to pull signal out of the noise. But it is possible in some cases; the rates of lung cancer for long time smokers being one of the best socially relevant examples. And yet this itself illustrates and important caveat: there are those who don’t seem to have any of the environmental risk factors for lung cancer who nevertheless develop lung cancer. I know this in part because there are individuals who report that once they are diagnosed with lung cancer others whom they encounter begin to subject them to a battery of questions relating to whether they ever smoked, or, whether they lived with a smoker, because the impression is that this sort of cancer demands a lifestyle prior.

Why? An effect demands a cause. This is a common cognitive bias, and we regularly extract spurious patterns to establish transparent causality on the world. Ultimately there is causality…but it is not always so transparent. A lot of biological process is subject to noise and randomness at the level of our perception. Consider that inbred isogenic lineages of simple organisms kept under perfectly homogenized environments such as C. elegans still exhibit phenotypic diversity. Stuff happens for a reason, but we will never really know what the reason is. So we bracket that under “random.”

And this is probably true for cancer as well, and that is tragic and results in existential crises. The real answer to the question “Why me?” is quite often “No one knows, no one will ever know.” It may be that some cancer are due to clear and causal environmental inputs. But almost surely much of it is outside our practical control. On the margin George Johnson may be wrong (e.g., cancer rates may be 10% higher than the past due to toxic chemicals), but in the broader point that cancer has been a biological fact of multicellular existence which strikes somewhat randomly, I believe he is probably right.

This is not an emotionally palatable answer, so Johnson will remain on the receiving end of many attacks for some time to come. He bears a message which is deeply disquieting for the human need for order and just deserts.

  • Robert Ford

    Is it worth buying the issue or is that the gist of it? here’s George talking it out:
    I remember way back when he first started researching for it he hit me with some amazing stat like only 8% of smokers get lung cancer or something like that.

    • razibkhan

      well, if you buy the magazine it contributes to me getting paid :-)

    • Sandgroper

      What does not seem to be commonly understood is that prolonged exposure to high concentrations of radon is thought to be a risk factor; radon occurs from the natural decomposition of uranium-bearing rocks like granite and some limestones, which are distributed very widely, and has always been around. It is just one example of how someone who has never had any exposure to tobacco smoke can be at elevated risk for lung cancer; but if someone contracts lung cancer, it seems to be assumed by many people that it must have been caused by some form of exposure to tobacco smoke. Mention radon and they seem never to have heard of it. And yet I’ve been told by an American colleague that radon exposure has been a pretty major public issue in the USA, to the extent that you could buy radon meters at gas stations to check out radon concentrations in your own house. It has certainly been a public issue in some parts of the UK where high radon concentrations occur.

      The slight catch is that there does seem to be a synergystic effect between smoking and radon exposure, but it’s not an absolute. People who have never had exposure to tobacco smoke can die of lung cancer. It happens. But that just seems to surprise a lot of people.

      • Robert Ford

        yeah my grandmother died of lung cancer but had never smoked and had never been around smoke. it’s hard to tell for sure though because everyone smoke back then so could be just from restaurants and hospitals

        • Sandgroper

          Robert, I’d be interested to know the geology of the area she lived in, and what her house was made of.

          • Robert Ford

            she lived in various housing in the suburbes of Detroit, Michigan, USA for almost her whole life. I know lower Michigan is a high risk radon area and i was going to get my home tested until I heard the same talk i referenced earlier with george in it. If I remember correctly, one of them mentioned that the radon detection industry was a “crock” and they were fear mongering people for profit. I checked it out and I sort of believe them. From what I’ve read you have a very small chance of actually having a problem with it. What do you think?

          • Sandgroper

            I’m suspicious of people who say that in the absence of tobacco smoke the risk is ‘negligible’. You’re breathing a radioactive gas. I’m also suspicious of talking about building or retrofitting ‘radon-proof’ buildings, which are impossible to achieve – particularly when the buildings themselves are sitting on top of hot rocks or built using radon-generating rocks, like using granite aggregates in concrete, or have internal stone wall facings or floorings. I think that may be where people get taken down – that a costly ‘retrofit’ of a building to make it ‘radon proof’ is a crock. You can’t – for one thing, it means totally sealing the building against ingress by a gas, and for another a lot of the radon can be generating inside the building from internal sources, and you have just made it radon proof to keep it all in.

            The answer is good ventilation, not trying to seal your house against radon ingress – particularly if your building was constructed of concrete that used granite as aggregates, and big expanses of internal facing stone and flooring.

            And if it has a basement, that’s an obvious area to pay attention to, or any inadequately ventilated room where a heavier-than-air gas could accumulate high concentrations.

            I know one guy who tested and found very high concentrations of radon in the basement of his own house, and he solved the problem completely by installing a small cheap plastic exhaust fan. That was environmental engineer Dave Carrier, who tested buildings all over America and found the highest radon concentrations he had ever seen in the basement of his own house. Cost – installing one cheap plastic exhaust fan. The radon concentrations dropped to virtually nothing.

            The take home message is ventilate your living quarters and work environment, then quit worrying about it. Remember when Mom always used to insist on opening windows to get some fresh air in? She was right.

          • Robert Ford

            yeah I think what George was implying is that it’s kind of a binary thing. You’re there at risk or not at all and chances are that you’re not at risk. I agree that when you do have a problem with radon gas it causes cancer though

          • Sandgroper

            I’m not sure I understand what binary refers to in this case. I guess either you get lung cancer or you don’t – it’s binary in that way, but that’s not very helpful.

            I don’t see how risk can be binary, unless it is a function of genes, to the extent that either you have a genetic predisposition to getting lung cancer or not. I’d be surprised if it was a function of a few genes of large effect, such that that might be true.

            90% of all people who get lung cancer are tobacco smokers or former smokers. I think people confuse that and get the idea that a high % of all smokers end up getting lung cancer, whereas the true % is very much lower. (Which is not all that comforting, because smokers can also get all sorts of other stuff, like COPD. I guess in at least some cases, if they lived long enough they might get lung cancer, but they die of something else earlier.)

            The real question is, on the topic, what would the incidence of lung cancer be in an ancient population, in the absence of ‘modern’ environmental toxins, including tobacco smoke. The answer is not zero, because there is at least one ancient environmental toxin that long predates humans, or any form of life, that is a known risk factor, and that is a decay product of naturally occurring minerals in rocks. And it also looks possible that lung cancer could occur without any environmental risk factors as a necessary condition to amplify the risk of it occurring by random mutation.

            Radon is not the only one, of course. There are naturally occurring ‘background’ levels of all kinds of environmental toxins, e.g. heavy metals from minerals in rocks, plant toxins, natural fermentation (ethyl alcohol is also a known risk factor for a range of cancers, no matter how much wine lovers might try to fool themselves).

            I guess I should read George’s book.

          • Sandgroper

            It could be a function of rare mutations. Some cancers are, or they occur in some cases due to rare mutations. No environmental risk factors required, and it looks unlikely they make any difference, or much difference. I guess maybe that’s what George is referring to, if he is saying that the ‘risk’ is binary. I still don’t get it, though because, by definition, risk is probabilistic. If the hazard is a rare mutation, then in any population there is some (low) probability that each individual will have the mutation; if someone does, then there is some probability that the hazard will be realized, i.e. it will result in cancer occurring some time during that person’s life.

            I don’t see how that is binary – even in Angelina Jolie’s case, she was not guaranteed to get breast or ovary cancer; she was just at very high risk of getting it (80% is getting up towards certainty, but it’s still not 100%), and she opted to reduce her risk surgically. Her risk is still not zero, but it’s now very much lower.

          • Robert Ford

            my bad, i meant the actual radon when i said binary. forget i said binary, i’ll just go with “low risk” of it happening to your basement…and even lower of it actually effecting you. also, i could be attributing that to the wrong person – i think it was either George of John Horgan who mentioned it but that was several years ago.
            i mean, i don’t really know, obviously. it just seems to me like it’s not that big of a deal, relatively speaking, but i’m just eyeballing it. seems like it belongs in the “watch out for free radicals” or “make sure to floss every day” category to me.

          • Sandgroper

            Real data set: anomalously high incidence of lung cancer in non-smoking housewives (I.e. they don’t go out to work, so workplace environment is not a factor) who live in non-smoking households. The doctors have been scratching their heads for decades, trying to guess at all kinds do possible risk factors, like breathing the smoke from cooking oil (you breathe a lot of evaporated oil and stuff when you stir fry properly with a wok).

            I think a lot of people would just assume that the major risk factor must be a bit of incidental second hand tobacco smoke, and would ignore the fact that these cohorts of women live in an area of granitic geology with a high uranium content; that they live in buildings which have been measured to contain some of the highest radon concentrations ever measured anywhere in the world, and that prolonged exposure to high concentrations of radon is a known risk factor in the incidence of lung cancer.

            To me that’s a bit more serious than teeth flossing.

          • Robert Ford

            Yeah, I think he was saying that there’s a low chance of that being you. It’s a problem but only for a few

          • Sandgroper

            From the Wikipedia article on Radon: “According to the EPA, the risk of lung cancer for smokers is significant due to synergistic effects of radon and smoking. For this population about 62 people in a total of 1,000 will die of lung cancer” i.e. about 6%. That’s ball park not far off the 8% you quoted from George Johnson. And about 0.7 of a person per 1,000 will die of lung cancer due to exposure to radon in people who have never smoked – a lot lower, obviously, but that’s not zero or ‘negligible’. 7 x10e-4 is not ‘negligible’ in my book. If that were an industrial hazard it would be rated as being in the region where all practical mitigation measures would be required to reduce it.

            But hey, ‘natural’ is good right…Mother Earth would never do anything to harm us.

  • Joe Q.

    They’re just that — risk factors. They raise the probability of getting cancer, but not all the way to 100%, just as their absence doesn’t lower the probability of getting cancer to 0%.

  • Kevin Bonham

    From an immunologist’s perspective – the idea that “cancer has been a biological fact of multicellular existence which strikes somewhat randomly” is almost self-evident. A vast amount of energy is spent on cancer surveillance and elimination, despite the inherent risk of autoimmunity that such surveillance elicits. If cancer was a modern problem, there wouldn’t be so much selective pressure to avoid it.

  • AMac78

    The US EPA has online materials explaining the relative risk of radon exposure. (No link as I consulted them on moving ~6 yrs ago; after radon testing the new residence, did opt for simple remediation.)

    Radon’s mechanism of action comes if it decays adjacent to a living cell, thus the lung-cancer risk: an atom might fission while in an alveolus.

    At the EPA-defined threshold level, ~12 hr/day radon exposure was equivalent to a fraction of a pack a day smoker in terms of lifetime increase in lung cancer risk, IIRC. A reasonably airtight single-family house on high-uranium bedrock could yield radon levels five to ten fold higher than threshold, equaling 2 packs/day. Again, IIRC.

    After having pipes installed to draw air from under the slab with a low-power exhaust fan, I had the house retested. Radon fell to ~5% of prior concentration.

    Radon would be a “modern” form of cancer risk, in that few pre-20th-century residential structures would have been sufficiently airtight to achieve radon concentrations way above the biologically-irrelevant levels of outside air.

    • Sandgroper

      Pre-20th Century stone residential buildings in Cornwall are a major concern. In a lot of geology, living in a cave was probably not a great idea – but then, back then, on a scale of environmental risks, people no doubt had a lot more to worry about than radon exposure.


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About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at


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