Rethinking cancer risks

So much for New Year’s resolutions. That is the takeaway for many after reading a Johns Hopkins School of Medicine study that concluded that many, if not most, cancers in adults are the result of what the researchers call “bad luck.”

Those results are likely to change how we think about the risk of getting cancer — in good ways and bad. While many factors appear to be random, that is no reason to ignore the ways in which behavior can influence the incidence of cancer.

The study by medical statistician Cristian Tomasetti and cancer researcher Bert Vogelstein was largely a statistical exercise. They examined stem cell divisions in different tissues to determine how they correlated with the risk of cancer developing in those tissues. Stem cells are especially important because they constantly divide to repair damaged tissue.

In some cases, however, mistakes occur as the DNA in the cell replicates. Over time these small mutations accumulate, increasing the risk of cancer. In other words, the researchers found a powerful correspondence between particular types of cancer cells and rates of division: The faster the stem cells divide in a particular tissue, the greater the chance of developing cancer in that tissue.

Tomasetti and Vogelstein then tried to isolate the degree to which the mutations are random or are the result of environmental or lifestyle factors. They concluded that 22 of 31 cancers that they examined were primarily the result of random mutations; the remaining nine were created by environmental factors. To put it more bluntly, 70 percent of the mutations were random — what the authors call “bad luck.” That is an interesting and eye-catching phrase for the writers of headlines and press releases, but its use carries real risks of misinterpretation, willful or otherwise.

For example, 70 percent of types of cancers is not the same as 70 percent of all cases of cancer. This is important news, but it is not as striking as it may seem.

First, scientists have long reckoned that random mutations contributed to the incidence of cancer but they did not know how great that role was. Moreover, mutations alone do not determine cancer rates. A mutation must be retained to develop into a cancer and that cancer must be malignant.

In other words, there are intervening variables that influence the mutation.

Second, certain types of cancer, such as breast and prostate cancer, were excluded from the study because there are no reliable stem cell division rates to use for the calculations.

Third, and most important for the 30 percent of cancers that are not the result of random mutations, behavior matters — a lot. Smoking has a powerful impact on cell mutation, as does excessive exposure to sunlight.

In other words, the incidence of skin and lung cancers can be impacted. That is a reminder for the pessimists, fatalists and undisciplined among us who look for any excuse to avoid responsibility. There is ample epidemiological evidence that shows that stopping smoking, losing weight and avoiding excessive sunlight can reduce the risk of cancers. This study does not undermine or reverse those findings.

Equally important are genetic factors that can play a powerful role in determining whether an individual gets cancer. Some people are genetically disposed to susceptibility and for this group, the study’s findings are secondary. They should rigorously follow cancer detection and screening protocols and even expand their use to account for random causes.

If “bad luck” is responsible for the appearance of some cancers, then “good luck” might be equally responsible for an absence of cancers in individuals who engage in high-risk behavior. That seems like a slim reed to hang one’s health and happiness; these findings are not a “get-out-of-jail-free card” for bad behavior.

As Tomasetti explained, “If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others.”

The evidence does show that there is a need for research that focuses on early detection of cancers attributable to random mutations. Scientists have understandably honed in on factors that have a visible relationship with cancer, especially when the causality appears to be clear. It is hard to know what to look for when the cause of a cancer is random.

As one of the researchers explained, for some cancers there is no evidence of hereditary or environmental factors at work. Yet, the survival rate for cancer patients who identify the disease early in its development is much higher.

If most incidences of cause are the result of random mutations, however, then new tests have to be designed and new protocols established that cast a wider net: In many cases there are no “easy indicators” of risks.

According to one study, there were an estimated 217.11 cases of cancer per 100,000 adults in Japan in 2012, and an estimated 703,863 cases in total. That same study estimates 17.4 deaths from lung cancer per 100,000 adults in 2012, 13.5 deaths from stomach cancer per 100,000 adults and 94.8 deaths per 100,000 adults in total. Those numbers are too high. Better understanding of the “randomness” behind the appearance of cancer may, paradoxically, allow us to better identify, prevent and treat this scourge.