A new study revisits an analysis made by the same lab in 2015 about the role of random mutations on cancer. The analysis uses computer modeling to estimate how many cancers are the result of replication errors. The authors say their study provides a molecular explanation for the large and apparently unpreventable component of cancer risk that has long puzzled epidemiologists. A study by the same team a few years ago led to lots of debate about cancer prevention, and the role of ‘bad luck’ in cancer. Much of that was based on the original press release that said “two-thirds of adult cancer incidence across tissues can be explained primarily by ‘bad luck.’ ” Eventually, the release was edited to clarify that two-thirds of the variation across different cancers was due random mutations.
This time, the authors stress that their work “does not diminish the importance of primary prevention but emphasizes that not all cancers can be prevented by avoiding environmental risk factors.”
We asked Otis W. Brawley, M.D., chief medical officer,for his response to the new work.
“This study reaffirms what we have known about cancer for years, namely that many cancers occur not because of anything we did, but because of what we call ‘replication error.’ Replication error can be compared to a genetic game of telephone, where imperfections accumulate until the message is no longer correct. They use a hypothetical example that even people living on another planet where the environment is perfect, there would still be a baseline number of “unavoidable” cancers due to replication errors.
“The study also reiterates the importance of two other major factors associated with cancer: heredity, and environment. Note that when epidemiologists talk about ‘environment,’ they’re referring not to exposure to toxins alone, but also to things like nutrition, physical activity, passive or direct smoking, sunlight, and other factors people are exposed to in their daily lives.
“The authors acknowledge that there is frequently a mix of these three influences: replication, heredity, and environment and that they can differ for different cancers under different circumstances.
“They calculated the impact of replication error by using a mathematical model to figure out how many times a cell would have to replicate before a random error would cause a cancer to start growing.
“Their initial report several years ago was met with lots of debate. This time, the authors explained the affect with caution and credibility, which should help clarify their conclusions in a way that will find a more receptive audience.
“The findings may lead to additional discussion of the role of ‘bad luck’ in cancer, but in fact the findings confirm something scientists have been talking about for a long time; that someone can do all the right things and still get cancer. This idea applies not only to people whose cancers are the result of replication error, but also to inherited genetic factors.
“While it would be easy to become fatalistic and think there’s nothing to be done about many cancers, in fact the paper reiterates the importance of primary prevention by avoiding environmental risk factors as well as ensuring everyone has access to proven early detection and screening, so we can find those cancers early and intervene in hopes of reducing their impact.”