About a year ago, a study published in the journal Science received a lot of attention and comment because it seemed to suggest that most cancers were mainly the result of random mutations or “bad luck.” I wrote about the study, including what commenters identified as some of its major weaknesses, in a post last January on Cancer Risk and “Bad Luck.”
A new study by a different team, published recently in Nature, revisits the question. It expands on the analysis in last year’s study and examines the question using several different approaches. It arrives at the conclusions that the development of cancer is heavily influenced by external factors.
Last Year’s “Bad Luck” Study
The study published last year–by researchers at Johns Hopkins University– found 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”. They concluded that early detection is the best way to prevent deaths from most types of cancer.
Commenters identified important weaknesses in that study. A prominent weakness was that two major types of cancer that have very high incidence rates–breast cancer and prostate cancer–were excluded from the study. Another major problem was that the study focused only on differences in cancer risk across various sites in the body but didn’t get down to what is causing all those cancers in the first place.
The New Study and Its Findings
The authors of the new study–a team at Stony Brook University in New York–were also troubled by some of the weaknesses in the Hopkins study. They wondered in particular whether the rate at which stem cells divide in the body is itself affected by external environmental exposures.
So, to investigate this, the team looked at the question several different ways. First, they ran different mathematical models looking at cell division rates. They based their work in part on the same data as the earlier team but also included breast cancer and prostate cancer–two very common cancer types that were not included in the earlier study.
The researchers also analyzed the “mutational signatures” present in cancer, which they described as the “fingerprints” left on cancer genomes by different mutational processes. They found that the majority of cancers have large proportions of mutations linked to exposures from carcinogens.
Finally, the researchers examined the epidemiological evidence. For example, they noted that more developed countries have much higher rates of breast and prostate cancer than less developed countries. But when people migrate from countries with lower incidence of these cancers their rates of these cancers quickly catch up to match those of people born there.
Overall, the researchers report that their analysis shows external or environmental factors contribute 70 to 90 percent of the risk of cancer developing over a person’s lifetime.
“Cancer experts not involved in either study generally praised the new paper,” writes Sharon Begley in Stat News, the Boston Globe’s life sciences publication, going on to say:
Several described its use of four different lines of evidence as “compelling” and called it a useful corrective to the meme that most cancer is the result of bad luck rather than carcinogens that can be minimized through either personal behavior or public policy.
“In general terms, the conclusion [of the new paper] is robust,” cancer epidemiologist Paul Pharaoh of the University of Cambridge told Britain’s Science Media Centre. Biostatistician Kevin McConway of England’s Open University said he was “impressed,” calling it “pretty convincing evidence that external factors play a major role in many cancers.”
What Are the Implications of the New Study?
Some commenters had feared that last year’s study and the notion that had been drawn from it that most cancers are mainly the result of “bad luck” could have weakened enthusiasm for preventive efforts. And in fact the authors themselves had concluded that finding cancer earlier, i.e., “early detection” would be more effective than preventive efforts.
In contrast, the findings from the new study reinforce the importance of cancer prevention as public policy. As individuals, we cannot “prevent” cancer. Yes, we can take measures to reduce our risk somewhat by emphasizing healthy behaviors such as exercising and maintaining healthy body weight–these lower our risk for many diseases, not just cancer.
But the personal behavior side of the cancer risk equation is overemphasized in our culture. Not only is this emphasis misleading as to how much influence we have as individuals on our risk for most types of cancer, it can lead to a mistaken sense that our actions somehow contributed to our getting cancer.
Several distinguished panels in recent years have evaluated the evidence regarding the contribution of environmental exposures to cancer risk. These include the President’s Cancer Panel (2009) on “Reducing Environmental Cancer Risk:What We Can Do Now,” the Institute of Medicine (2011) on “Breast Cancer and Environment: A Life Course Approach,” and the Interagency Environmental Research and Coordinating Committee (2013) on “Breast Cancer and the Environment: Prioritizing Prevention.” Each of these panels has included in its report recommendations for action in response to that evidence.
Among the recommendations of the President’s Cancer Panel was the need for additional research on the environmental causes of cancer, in particular the consequences of cumulative exposures over a lifetime and the interaction of multiple environmental contaminants. That panel also stressed the need for more effective measurement methods and toxicity testing procedures and the need to both enforce and update regulations governing environmental contaminants.
It’s past time to implement the recommendations clearly identified and agreed upon by these panels of experts. This new research further underscores the importance of environmental factors in cancer and the opportunity to save lives through responsive changes in public policy.
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