Cancer Risk and “Bad Luck”

Are a large proportion of cancer cases mainly the result of “bad luck”? That is certainly the impression given by recent media reports about a study conducted by researchers at Johns Hopkins University and published in the journal Science.

What did the researchers do and what did this study actually show? Is it really time to reconsider our understanding of cancer and its causes?

The study and its findings

It has long been recognized that some cancers likely arise, at least in part, as a result of random genetic mutations that occur as cells in the body divide over the course of a person’s lifetime. The authors of this study* wanted to try to quantify this effect and find out just how much cancer risk is related mostly to these random genetic mutations.

The researchers began by noting that stem cells in different parts of the body divide at different rates. They compared the known rates of stem cell division in various body tissues or organs with the corresponding U.S. incidence rates for the respective cancer types. What they found was that there was a fairly close correlation overall between the rate of stem cell division in a body tissue and the frequency of cancers developing there.

Based on this finding, using a statistical calculation, the researchers estimated that roughly two-thirds of the variation in cancer risk across tissue types arises from random mutations.

The researchers say their findings indicate that more emphasis should be placed on early detection, and that the best way to prevent deaths from most types of cancer (those that do not have major known hereditary or environmental contributing factors) is to “detect them and treat them early, while they are still curable.”

What does all this really tell us?

Various commentators have pointed out that there are a number of weaknesses in this study and its methodology.

One important weakness is that two major types of cancer that have very high incidence rates–breast cancer and prostate cancer–were excluded from the study. They researchers say they were unable to include these cancer types because they could not find reliable stem cell division rates for them in the scientific literature. Other frequently occurring cancers that were not in the study included uterine cancer, bladder cancer and kidney cancer.

A second problem is the lack of a clear understanding of the reasons why rates of stem cell division differ across tissue types.

The authors attributed the differences in stem cell division rates to randomness or “bad luck”. But commenters have pointed out that more research is needed in order to understand these differences. The Wall Street Journal reported this input from an expert:

Habibul Ahsan, a professor of epidemiology, medicine and genetics at University of Chicago Medical Center, called the research intriguing but said it was weakened by the lack of data on breast and prostate cancer, two of the most common forms of cancer. He also said more research needs to be done into why stem cells in various tissues divide at different rates–differences that both he and the Johns Hopkins researchers said could be influenced by environmental or inherited factors.

Another issue, emphasized by Silent Spring Institute in their commentary on the study, is that variations in cancer risk across organs don’t explain what is causing all those cancers in the first place:

It’s troubling to estimate bad luck from a worst case. The U.S. today has among the highest cancer rates in the world. (Is that very bad luck?) The study considers the risk of getting cancer per stem cell division for people in the U.S. now, but that ratio is not immutable and is different for different populations. The relationship between the number of cell divisions and the chance of getting cancer is influenced by environment, lifestyle and genetic factors.

We already know that cancer arises as a result of the complex interplay of a variety of factors, including inherited susceptibility (in some cases) as well as hormonal and other internal biological factors, external environmental factors and random genetic mutations that occur over a person’s lifetime. That is why no one should ever feel that they are somehow responsible for their cancer–cancer is just too complex and no one thing a person did or didn’t do can ever be labeled as “the cause” of their cancer.

We also already know there are actions that individuals can take to reduce their risk for some types of cancer, as well as other diseases. These include not smoking, maintaining a healthy body weight and maintaining appropriate levels of physical activity.

But do we have a better idea now of just how much cancer risk is related to random genetic mutations? I don’t think we can say that, because we just don’t know that there aren’t important–and modifiable–factors driving, at least in part, what seems to be “random”. A critical part of the story is external environmental factors, where we already have some insight from many studies about links between toxic exposures and increased cancer risk.

What this comes down to is that the necessary research needs to be carried out so that we can have a more comprehensive understanding of the drivers of cancer risk. And, most importantly, we need to take the appropriate public policy actions as a society to reduce those exposures and risks and save countless lives.

*Only an abstract of the study is freely accessible online. I was able to obtain a copy of the full article at a local university library.

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