Evidence / Health

The Facts of Random Chance and Cancer Prevention

I spend a lot of time researching and teaching about cardiovascular disease (CVD), and I have found over the years that my students view CVD similarly: as the fault of the individual. Although this isn’t true (there are unmodifiable risk factors for CVD such as menopausal status, gender, age and heredity), many students perceive that unhealthy lifestyle habits such as poor diet, physical inactivity and smoking cause CVD, and therefore the outcomes– heart attacks, strokes, heart failure– are largely caused by the personal failings of the patient. By contrast, large numbers of my students feel that cancer, with the apparent randomness of cause and occurrence, is a much more sympathetic disease: it can happen any time, to anyone, independent of personal actions, and thus is a pathology for which they have much more empathy.

A fascinating recent study in the journal Science explored whether this belief in the randomness of cancer is validated. As study authors explain in their introduction, only about 5-10% of cancers are explained by genetic or hereditary components. This leaves the obvious contributor as environmental risk factors (e.g., smoking, or exposure to carcinogens), yet these risk factors do not often successfully predict cancer risk. Graph Taken from Tomasetti et al. 2015The authors propose a novel hypothesis: tissues with cells that divide frequently, with high replication rates of DNA, are more prone to  spontaneous mutations leading to cancer. In support of their hypothesis, authors show a strong relationship between the lifetime cancer risk and number of stem cell divisions in a tissue such that approximately 65% of the difference in cancer risk between various tissues may be explained by the rate of DNA replication.

Moreover, authors then calculate an Extra Risk Score (ERS) to divide cancers into those that occur in part because of hereditary and environmental factors (in other words, prone to high ERS because of the influence of additional factors) vs. those that occur largely due to spontaneous, uncontrollable mutations alone (low ERS). Graph taken from Tomasetti et al. 2015
As you can see from the attached graph, cancers portrayed in blue (high ERS) are those that are influenced more substantially by lifestyle and hereditary factors, such as lung cancer. Cancers portrayed in green (low ERS) are those largely attributable to spontaneous mutations in tissues with high stem cell division rates. Why is this important? Because this finding has the potential to drive public health efforts at cancer prevention and treatment. Primary prevention (i.e., reducing cancer risk) should focus on the blue cancer risk group, whereas secondary prevention (i.e., improving detection and treatment) should focus on the green cancer risk group.

To conclude, the public perception that cancer is a random, uncontrollable disease is supported in part by research. But, our prevention, treatment and detection efforts don’t have to be random, and data are a powerful tool with which to lead that effort.



One thought on “The Facts of Random Chance and Cancer Prevention

  1. This is so interesting. So often I hear from people: I’m not worried because I don’t have cancer in my family. I worked in a lab at the Dana Farber many years ago, and it was always my impression that there was a lot more randomness in cancer stats than people imagined. I think we like to imagine that we have control over our health status — and if we just do the right things, we’ll be safe. Anyone looking at the cancer wards at DF and Boston Children’s would get a really different impression. The graph is also very interesting — delineating which cancers its actually worth worrying about. Finally, I think the DNA replication idea intuitively makes a lot of sense. We’ve long known that fast dividing cells are more susceptible to cancer — and that cancer drugs (at least alkylating agents) attack cancer because of its relatively rapid division vs other somatic cells…but the idea that division cycles themselves are the engine of mutations seems completely logical. If we can measure random mitochondrial mutations between ethnic groups as a “clock” for human difference, wouldn’t we also expect that fast dividing cells would be, in effect, aging faster, acquiring more mutations over time? Really interesting stuff.

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