The Most Powerful Carcinogen Is Entropy

By George Johnson | July 7, 2013 4:27 pm

I was at science writers’ summer camp last week (I’ll probably write more about that later) when Razib Khan, on his blog Gene Expressions, wrote about my forthcoming book,  The Cancer Chronicles: Unlocking Medicine’s Deepest Mystery. It’s a thoughtful post, and I was particularly struck by his observations about cause and effect — how the human mind demands reasons, preferably simple ones, even when none may exist. That is one of the obsessions behind Fire in the Mind (the book and the blog), and it carries over to The Cancer Chronicles.

When we or someone we love gets cancer, we agonize over the reasons. Was there something we did wrong or that was done to us? When we hear about strangers who are stricken, we want to believe that they ate too much junk food or lived in a particularly polluted atmosphere — mistakes we personally can avoid. But more often than not there is no identifiable cause.

In chapter 3 of the book, “The Consolations of Anthropology” (it is excerpted this month in Discover), I describe evidence from the fossil record showing that cancer has been part of life since the beginnings of humankind (and long before — my first chapter is about a dinosaur with a metastatic bone tumor). That in itself is not surprising. There are a hundred trillion cells in a human body. During any one second, several million of them are dividing. With each division, the entire genome is copied and passed along to the daughter cells — which go on to divide and pass the information to the next generation. And the next, and so on down the line.

Only a believer in a perfect creation could believe that errors do not happen along the way. In fact they occur with each division. Most are either harmless or they kill the cell outright. Others are caught by the genetic safeguards that have evolved over the millennia to recognize and remove damaged cells. But mistakes still get through — as they must, for without genetic mutations life would not evolve.

Cancer happens because some of those mutations, in the right combination, can cause a lineage of cells to start expanding and evolving on its own, independent of the welfare of the body. It burgeons into a tumor, and as it grows it acquires — through random variation and selection — the traits it needs to survive, expand, and colonize the body. It becomes a quasi-creature driven by the Darwinian dictate to become fitter and fitter. To be fruitful and multiply.

Cancer and life itself are both the result of mutations. Most of these appear to be spontaneous — the result of entropy — while others can be traced to carcinogens: natural ones like sunlight and manufactured ones like the estimated 80,000 substances that have been introduced over the decades by the chemical industry.

Most of these, by far, have not been tested for carcinogenicity, and regulation has been lax. Yet decades of epidemiological studies indicate that — except for the carcinogens in cigarette smoke — synthetic chemicals, including food additives, are not a major contributor to the overall cancer rate. However toxic a substance may be, the amount of exposure received by the general population is very dilute. Each year, as more novel substances have been unleashed into the world, the overall cancer rate has remained steady and, for the last two decades, has been declining. In the United States, only two residential cancer clusters have been identified and associated with pollutants. But as I’ve written elsewhere, even these are far from clearcut and they involve a handful of cancer cases.

None of this means that dumping toxic waste is not a crime against the earth and its creatures or that the transgressors should not be prosecuted. Every effort should be made to reduce potential toxins. (I’m belaboring these points because I know how easy it is to be misunderstood.) But in seeking out the essence of cancer, scientists have had to cast a much wider net.

In my book I describe a landmark study — “The Causes of Cancer” by Richard Doll and Richard Peto — which concluded that “most of the types of cancer that are common today in the United States must be due mainly to factors that have been present for a long time.” The big exception was lung cancer caused by cigarettes. Over the years, followup studies have reached much the same conclusion. Here is a chart, from a 2012 report by the American Association of Cancer Research, that breaks down the causes by percentages:

From the AACR Cancer Progress Report 2012.

All charts like this oversimplify. Any individual case of cancer involves multiple factors. Chain smokers tend not to exercise much — and you can smoke all your life without getting lung cancer. It takes multiple mutations for a cell to become malignant, and each mutation might have a different trigger. Some mutations will be inherited — these are involved in 5 to 10 percent of cancer cases — but most will be the result of random copying errors.

I find myself reacting to that realization in conflicting ways. Here is how I put it in the book:

There is something comforting about knowing that cancer has always been with us, that it is not all our fault, that you can take every precaution and still something in the genetic coils can become unsprung. . . . But there is also comfort in believing that humans, through their own devices, have increased the likelihood of cancer. What free-willed creatures have created can conceivably be undone. Failing that, there is at least a culprit to blame.

If only we could find it.

Related post: The Hunt for the Prehistoric Roots of Cancer

Follow me on Twitter @byGeorgeJohnson

  • http://slartibartfastibast.tumblr.com/ slartibartfastibast

    “Cancer happens because some of those mutations, in the right
    combination”

    Most cancers aren’t traceable to specific genetic mutations:

    “Prostate cancer is the second leading cause of cancer-caused fatalities
    in men, and within a man’s lifetime, one in six men will have the
    disease. […] Hypermethylation of the CpG island within the promoter region of the GSTP1 gene has been found to occur in more than 90% of prostate cancers.”
    https://en.wikipedia.org/wiki/Cancer_epigenetics

    More info: http://www.youtube.com/watch?v=yoQYh0qPtz8

    • http://talaya.net George Johnson

      Thanks for your comment. You are right that scientists are uncovering epigenetic influences, but cancer still appears to be largely a genetic phenomenon. Here’s an overview for prostate: Prevalent Mutations in Prostate Cancer. Some of the mutations are inherited: Genetics of Prostate Cancer.

    • byGeorgeJohnson

      Thanks for your comment. You are right that scientists are uncovering epigenetic influences, but cancer still appears to be largely a genetic phenomenon. Here’s an overview for prostate: Prevalent Mutations in Prostate Cancer. Some of the mutations are inherited: Genetics of Prostate Cancer.

      • http://slartibartfastibast.tumblr.com/ slartibartfastibast

        “cancer still appears to be primarily a genetic phenomenon.”

        That was in 2005. Hypomethylation can lead to mutations in specific parts of the genome, but those are an effect rather than a cause of the cancer that results. Most cancers are epigenetic in origin (we just didn’t have the sequencing tech to be able to see this a decade ago):

        “Our data show for the first time that hypermethylation of HIC1 promoter results in loss of its repressive function, responsible for prostate cancer progression and invasion.”
        http://clincancerres.aacrjournals.org/content/19/6/1400.abstract

        “The association between DNA hypomethylation and the presence of metastases was statistically significant (P = 0.044), and both chromosomal alterations and DNA hypomethylation tended to be more frequent in higher-stage tumors.”
        http://onlinelibrary.wiley.com/doi/10.1002/gcc.10092/abstract

        • byGeorgeJohnson

          Thanks. The book will be out in August. I get into epigenetics in chapter 9. It’s a fascinating subject.

  • http://blogs.discovermagazine.com Carol Thompson

    Doll and Peto and their followers, including the Surgeons General, are guilty of scientific fraud for ignoring the role of infection in order to blame peoples’ lifestyles. Poorer people are more likely to have been exposed to the pathogens that are the real causes of cancer due to crowding and the fact that the people around them are more likely to carry those pathogens. This gives the Doll & Peto crowd a pretext to bash all those things the poor people do and wage a culture war against them. Their pie chart with its scanty portion allocated to viruses is a complete fraud. It should really be not less than 20%.

    http://www.smokershistory.com/percent.htm

    • http://talaya.net George Johnson

      A conspiracy so immense!

    • byGeorgeJohnson

      Infectious agents, bacterial and viral, can indeed trigger some cancers. For a discussion (without an accompanying conspiracy theory) see this report by the World Health Organization: http://www.ncbi.nlm.nih.gov/pubmed/16404738.

      • http://blogs.discovermagazine.com Carol Thompson

        The proportion in the WHO estimate is far higher than that tiny sliver of around 5% in the Doll & Peto pie chart. That WHO estimate is low. No lung, bladder, or esophageal cancers were attributed to HPV. The role of JC polyomavirus in colon cancer isn’t discussed, either.

        Only 85% of liver cancers were attributed to HBV and HCV; “the relative risk of liver cancer due to infection with hepatitis B is based on measurement of serum HBsAg. However, viral DNA can be found in many liver cancers without evidence of infection based on HBs antigenaemia or antibody to HCV” (WHO). It should be 94% or more, based on studies which not only found the DNA but determined that it was associated with increased risk of liver cancer.

        HCV has also been implicated in lymphomas, and HBV and Helicobacter pylori have also been implicated in pancreatic cancer.

        In EBV and nasopharyngeal carcinoma, he parrots the fallacy that keratinizing types are “less often infected,” and knocks 2% off the total of NPCs. Versus Pathmanathan 1995, “all types of NPC, regardless of histological type or differentiation contain clonal episomal EBV genomes, express specific EBV genes and are a clonal expansion of EBV-infected cells.”

        http://www.ncbi.nlm.nih.gov/pubmed/7778675

        EBV has also been implicated in breast cancer and about 10% of gastric cancers. But the National Toxicology Program still hasn’t even admitted that EBV is a human carcinogen, although the IARC did so in 1997. Subsequently, in 2011, the NTP proclaimed that formaldehyde causes NPC, with a mere passing mention of EBV which ignored the vast body of research, and without input from anyone with expertise on the role of EBV (or any other virus) in human cancer. So, it’s a mere pretext to regulate, meddle, and ban, yet neither industry nor any supposed opponent of bad science ever calls them on it.

        The Surgeon General reports are even more flagrant in their evasions of the role of infection. They need formaldehyde as one of the purported carcinogens in cigarette smoke, and this supplies them with the “science.” And you think there’s no conspiracy!

        • http://blogs.discovermagazine.com Carol Thompson

          Here’s what the National Cancer Institute does. According to experts who’ve actually investigated viruses in liver cancer, markers of hepatitis viruses B and C were not found in only 6.2% of American cases, and about 5% overall. “Importantly, among 125 intrahepatic HBV DNA-positive patients, 44 (35.2%) were serologically negative for HBsAg (occult hepatitis B). Furthermore, 15.5% of HCC patients (9/58) who were negative for all HBV markers had intrahepatic HBV DNA.”

          http://www.nih.go.jp/JJID/56/12.pdf

          But the National Cancer Institute is using a deficient database to falsely blame obesity for liver cancer. They claim that only 7.3% of cases had HBV, 18.3% had HCV, and 3.3% had unspecified viral hepatitis (total 28.9%). (Even these grossly underdetected proportions resulted in adjusted odds ratios of 19.87 (16.76-23.57), 62.92 (55.39-71.46), and 13.46 (10.68-16.97).) Their claim that “20%-50% of HCC cases remain idiopathic” is based on the same faulty data.

          http://onlinelibrary.wiley.com/doi/10.1002/hep.24397/full

          And here’s the propaganda payload. Based on the defective SEER database, they falsely claim that “Among individual factors, diabetes/obesity had the greatest PAF (36.6%), followed by alcohol-related disorders (23.5%), HCV (22.4%), HBV (6.3%) and rare genetic disorders (3.2%)… Overall, eliminating diabetes/obesity could reduce the incidence of HCC more than the elimination of any other factor.”

          http://www.ncbi.nlm.nih.gov/pubmed/23752878

          And it’s pure hogwash.

    • Buddy199

      Tobacco, excess weight and lack of regular exercise are all the result of choice.

    • http://blogs.discovermagazine.com Carol Thompson

      I should have added that the so-called “landmark study” by Doll & Peto was published in 1981. This means it had ZERO consideration of the role of infection in cancer. It’s a monument to ignorance, 32 years out of date, and there has been a mountain of research on infection since then. Yet they’ve been allowed to get away with peddling their lifestyle twaddle, coasting along in their political juggernaut, borne on the servile shoulders of mass media who worship them like deities.

  • Buddy199

    Tobacco, excess weight, lack of exercise.

    The same risk factors for heart disease, stroke, diabetes.

  • Genevieve

    http://www.youtube.com/watch?v=1CN7PF10RKo

    One of the most comprehensive studies ever preformed looking at nutrition as a catalyst for cancer. If you have any concern about your health then you need to watch this clip and read The China Study by Colin T. Campbell

    • http://blogs.discovermagazine.com Carol Thompson

      Campbell is a cult leader who manipulates emotions and wishful thinking, not real a scientist.

    • Lah99

      I know Colin and he has been tooting that horn for decades. It’s a sour note with no data that can pass any degree of scientific rigor.

      • bccarver

        ditto

  • leelaplay

    Hi there. Your stats seem to be a bit off for viral causes. The World Health Organization, Jan 2013, reports that “cancer
    causing viral infections such as HBV/HCV and HPV are responsible for up
    to 20% of cancer deaths in low- and middle-income countries.About 70% of all cancer deaths in 2008 occurred in low- and middle-income countries.” And that is just the known viruses. Examining new possible viral causes of cancer is a rapidly expanding field.
    http://www.who.int/mediacentre/factsheets/fs297/en/

    • byGeorgeJohnson

      Thanks for the link. I believe the discrepancy comes from the fact that the AACR chart is for the United States. Viral infections leading to cervical and liver cancer are definitely a bigger problem in developing countries. It is a sad situation, but at least cancers caused by infectious agents stand a greater chance than others of being prevented. Another is stomach cancer caused by Helicobacter pylori. It’s a matter of persuading more developed countries to help provide the resources to do this.

      • Odin Matanguihan

        Assuming that hepatitis B could be transmitted through saliva, I would suspect culture plays a role in my country. Many of us drink socially in which it is like a social ritual. There is only one glass and one assigned person pours equal amounts. Everyone takes turns drinking from the same glass. Sometimes it may also involve people taking turns telling jokes/stories or singing at a videoke bar.

        Regarding H.pylori, I thought I read somewhere (probably this same website) that H. pylori is actually beneficial. One article says it is part of our signalling system while another says that the ones causing stomach cancer are actually themselves just responding to a viral assault.

  • DRRL

    “Only a creationist could believe that errors do not happen along the way,” is an unwarranted cheap shot. I know many creationists, both scientifically savvy as well as unlearned, and have never heard such a claim by any. Creating straw men does not serve scientific argumentation.

    • http://talaya.net/ George Johnson

      I’ve amended the sentence. Creationists do welcome entropy as a manifestation of the fall from Eden.

  • John Raguso

    I believe that Cancer Is caused by ‘ENTROPY’. But this leaves us with a weapon to use on the newly formed cancer cells—-proper dietary restriction, such as avoiding meat and or increasing cruciferous vegetables

  • mhj2013

    I have to point out that creationists most certainly believe in errors in the genome (casual creationists are likely just uninformed). In fact, there is a creationist book devoted the study of entropy in genetics: “Genetic Entropy & The Mystery of the Genome” by Sanford. There are also many articles regarding mutations in the genome on the Institute of Creation Research website (for example, “Creation, Mutation, and Variation” at http://www.icr.org/articles/view/171/296/).

    • http://talaya.net/ George Johnson

      Thank you for the comment. I’d be interested in learning how that fits in with biblical literalism. Are the entropic effects of random mutation seen as a manifestation of the fall from perfection beginning in the Garden of Eden?

      • http://talaya.net/ George Johnson

        Ah, I just found this statement on the Institute of Creation Research website: “the tragedy of cancer is the result of ongoing genetic deterioration in our body cells, and as such is a manifestation of the Edenic curse of decay and death.” http://www.icr.org/article/772/

        I’ve amended the sentence to read “Only a believer in a perfect creation . . .”

        • mhj2013

          I see you answered your own question, but I would have answered “yes.” In fact, the Bible talks about the second law of thermodynamics (i.e. entropy):

          Psalm 102:25-26 “In the beginning you laid the foundations of the earth, and the heavens are the work of your hands. They will perish, but you remain; they will all wear out like a garment. Like clothing you will change them and they will be discarded.”

          Romans 8:20-21 For the creation was subjected to frustration, not by its own choice, but by the will of the one who subjected it, in hope that the creation itself will be liberated from its bondage to decay and brought into the freedom and glory of the children of God.”

          Others: Isaiah 51:6, Matthew 24:35, 1 John 2:17

  • Izzy Evangelique

    This is a great article! I had a similar hypothesis about the relationship between cancer and entropy. In fact, entropy could potentially be causal to all forms of cancer, either directly or indirectly. Depending on our relationship to the environment, our genes are constantly being modified by internal and external pressures. Sometimes, a gene isn’t going to come out right.
    Just like a dance troupe, if a single individual falls out of step, the whole group could eventually degrade into arrhythmic behavior. However, there is always the possibility that an individual never gets cancer. Whether as a result of incredible genes, or incredulous luck, that fact is almost as impressive, and deserving of research, as the existence and threat of cancer, itself.

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Fire in the Mind

Whether a subtle new pattern shows up in an experiment on the Higgs boson, an epidemiological report about a suspected cancer cluster, or a double-blind trial purporting to demonstrate ESP, it can be maddeningly difficult to distinguish between what we see and what we think we see. "Fire in the Mind" takes a look at the big questions behind today’s science news.

About George Johnson

George Johnson writes about science for the New York Times, National Geographic Magazine, Slate, and other publications. His nine books include The Cancer Chronicles: Unlocking Medicine's Deepest Mystery (August 2013), The Ten Most Beautiful Experiments, A Shortcut Through Time, and Fire in the Mind. He is a winner of the AAAS Science Journalism Award and has twice been a finalist for the Royal Society science book prize. Co-founder and director of the Santa Fe Science Writing Workshop, he can be found on the Web at talaya.net. Twitter @byGeorgeJohnson.

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