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Cancer Care Chronicles
August 2015

The Implications of “Random Chance” in Cancer GenesisWhy Stochastic Can Be a Dirty Word

Author Affiliations
  • 1DeCesaris Cancer Institute, Anne Arundel Medical Center, Annapolis, Maryland
JAMA Oncol. 2015;1(5):575-576. doi:10.1001/jamaoncol.2015.0786

The recent publication in Science of calculations implying that oncogenesis is a “stochastic” (ie, random) process and that cancer results from “bad luck”1 was widely reported in the media.2 The poignant, often emotional comments that followed startled some3 but not those of us who care for cancer patients professionally. Years of patient interactions could have foretold that the “Why me?” question is an essential and sensitive subject for actual human beings living with cancer—and for loved ones left behind. The Science article reports no new experiments but rather extensive mathematical calculations with existing data from SEER (the Surveillance, Epidemiology, and End Results Program) regarding cancer incidence in different tissues and rates of stem cell division in those same tissues. Since DNA transcription errors are known to occur at similar rates in different tissues,1 the authors hypothesized that there should be a close correlation between stem cell division rates and cancer incidence rates if cancer is a result of random mutations to those stem cells. The authors found this precise correlation across cancers that vary in incidence by 5 orders of magnitude. They concluded that two-thirds of the difference in cancer incidence rates between types of tissue could be explained by random error during DNA transcription, or to use the authors’ own term, “bad luck.”

These calculations and conclusions will get the scientific scrutiny they deserve because, if valid, they have implications for the concept of cancer preventability and the public policies and funds that follow in consequence. The authors argue that cancer prevention can only be effective for the short list of cancers in which the ratio of observed to expected occurrences is high, for these are the only ones in which a genetic, toxic, or infectious factor might operate.

But it is not the public policy ramifications that concern me; rather, it is the personal ramifications for people with cancer. In interviews, one of the authors suggested that the findings were good news for some patients who need no longer worry that they did anything “wrong” to bring on their cancer, nor “stress out about every single thing or every action I take in my life, or everything I touch or eat.”2 But they also predicted that in a society that craves control, some would be uncomfortable when brought face to face with the recognition that the disease is outside our desired control.

However, a review of the hundreds of heartfelt comments made on the Science3 websites and on the websites of other media reporting the story reveals more complicated reactions.2 A taxonomy of these public responses is apparent: relief (as predicted by the authors of the article) that they did nothing to give themselves cancer, skepticism about the author’s motives, doubt about the accuracy of the science, a belief that the science must be wrong because cancer cannot be random, and anguish about their cancer being deprived of meaning. The last 2 responses often appear together. In an unscientific sampling, I found that the amount of anguish approximates the amount of relief.

That cancer should have a special meaning has not always been a welcome idea. Beginning in 1978, Susan Sontag4 vehemently argued against the notion that cancer had a personal meaning beyond that of other diseases. She dismissed the idea, then current, that there was a flaw in the cancer patient’s personality that created favorable conditions for the cancer to arise, which also implied that cancer could be prevented or cured with personality improvements. Sontag’s treatise described a long history of stigmatization involving diseases such as tuberculosis, syphilis, and leprosy. She wanted her disease (cancer) to be approached by society like any other without assigning it any special meaning: “Nothing is more punitive than to give a disease a meaning—that meaning being invariably a moralistic one.”5 In 1989, Barbara Boggs Sigmund,6 a woman with metastatic melanoma, felt obligated to respond to the prevailing notion that cancer patients somehow invited the disease. In a bold essay in the New York Times titled “I Didn’t Give Myself Cancer,” which was republished widely, she wrote “…evil, illness, accident, injustice and bad luck strike the self-improved and unimproved alike.”6

But the online commentators seem to desire meaning, if not the stigma that Sontag and Sigmund rebelled against. And it does not matter if the meaning is nonscientific. It is an uncomfortable irony that the very process—spontaneous mutations—that provides biological life its diversity and hence its durability, is also responsible for disease that results in premature death in so many. Because “random variation…is the engine of evolution,”7 cancer may be the price our species (and other species too) must pay for the adaptability of life. Irony aside, how do we counsel our patients on this issue, whether or not they have read Science magazine?

The way to address this is to reconcile the 2 views: bad luck among the stem cells does not imply that the cancer, or the life it affects, has no meaning. The process may be random, but the meaning is in the life and not the disease process. The meaning is in the cherished families, friends, and life’s work left behind. Certainly, we should heed the lessons of epidemiology with regard to behaviors, but let us lift the burden of cancer diagnosis and survivorship from our patients’ shoulders. Cancer is an intricate and complicated biological process. People do not die from it because they are weak soldiers.

Let us advise wariness in the face of societal messages that demand extremes of diet, weight, intake of natural or unnatural substances, exercise, attitude, and an avoidance of stress—whatever that means. Perhaps one day some of these factors will be linked to a reduction in DNA transcription errors—or just as likely, an increase in them. In the meantime, abjure the colonic enemas.

It is perfectly fine for cancer in the abstract to be stochastic; but cancer in the individual should not be deprived of meaning. We need not reject the randomness of mutation-caused cancer, if that is where the science leads, but we can still believe in the deep meaningfulness of the cancer-affected life.

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Article Information

Corresponding Author: Barry R. Meisenberg, MD, DeCesaris Cancer Institute, Anne Arundel Medical Center, 2001 Medical Pkwy, Annapolis, MD 21401 (Meisenberg@aahs.org).

Published Online: May 7, 2015. doi:10.1001/jamaoncol.2015.0786.

Conflict of Interest Disclosures: None reported.

Tomasetti  C, Vogelstein  B.  Cancer etiology: variation in cancer risk among tissues can be explained by the number of stem cell divisions.  Science. 2015;347(6217):78-81.PubMedArticle
Grady  D.  Cancer’s random assault.New York Times. January 6, 2015. http://www.nytimes.com/2015/01/06/health/cancers-random-assault.html?_r=0. Accessed March 25, 2015.
Couzin-Frankel  J.  Bad luck and cancer: a science reporter’s reflections on a controversial story.Science. January 2015. http://news.sciencemag.org/biology/2015/01/bad-luck-and-cancer-science-reporter-s-reflections-controversial-story. Accessed March 25, 2015.
Sontag  S.  Illness as a Metaphor. New York, NY: Farrar, Straus and Giroux; 1978.
Sontag  S.  Illness as a Metaphor and AIDS and Its Metaphor. London, England: Penguin Books; 1989.
Sigmund  BB.  I didn’t give myself cancer. New York Times. December 30, 1989.
Johnson  G.  Random chance’s role in cancer. New York Times. January 19, 2015. http://www.nytimes.com/2015/01/20/science/though-we-long-for-control-chance-plays-a-powerful-role-in-the-biology-of-cancer-and-the-evolution-of-life.html?_r=0. Accessed March 25, 2015.