The cause of cancer has been debated within the scientific community ever since the discovery of the disease. Some researchers claim that cancer is caused by intrinsic risk factors, such as DNA replication errors that can occur during cell division; others claim that the disease is caused by intrinsic risk factors such as smoking or ultraviolet light exposure.
While it is widely accepted that both intrinsic and extrinsic risk factors cause cancer, a recent Stony Brook University study, published in the journal Nature, found that about 80 percent of cancers are caused by various extrinsic risk factors.
An earlier paper published in the journal Science concluded that the two-thirds of cancer occurrences can be attributed to intrinsic risk factors, giving rise to the “bad luck” theory that extrinsic factors such as environment and behavior have little effect on your chance of getting cancer. Song Wu, an assistant professor in the Department of Applied Mathematics and Statistics, and his research team set out to prove that extrinsic risk factors indeed play a major role in causing cancer.
“Bad luck, which is an error occurring during cell division, is something that you really can’t control,” Wu said. “That part contributing two-thirds to the human cancer risk is of course a huge implication to society. It’s basically saying that cancer prevention is not as effective as you think. People have to eat healthy, live healthy and even if you live in a bubble in a completely clean environment, you can still only reduce one-third of the risk.”
Not only would this theory impact the way people choose to live their lives, but it would also have an impact on healthcare policy. It would cause a shift in focus from cancer prevention to early detection and treatment of cancer.
To determine if the majority of cancer is caused by “bad luck” or by external risk factors, Wu and his research team developed four distinct approaches to analyze and assess cancer risk.
First, the researchers compared the occurrence rate for cancers that originate in parts of the body that go through the process of cell division at the same rate.
“Every cell uses the same mechanism to replicate the DNA during cell division, so we assume that the replication error rate is pretty much stable across all tissues,” Wu said. “If two tissues have about the same cell division rate, they should share the same intrinsic risk.”
From this comparison, Wu found that some cancers had a higher risk of developing than others with similar cell division rates. This clearly demonstrates that extrinsic risk factors play a significant role in the development of some cancers.
The team also analyzed the SEER (Surveillance, Epidemiologic and End Results) database, finding that many cancers have been increasing in occurrence since the ’70s. Cells have not been dividing at a faster rate over the past 40 years, indicating that extrinsic risk factors have lead to the increased occurrence of certain types of cancer.
Wu and his collaborators also went through the literature on mutation signatures of specific cancers. Many different cancer types have a particular mutation that can be considered a “fingerprint” of certain extrinsic risk factors.
“Smoking and UV will induce a different mutation type, this is a so-called mutation signature,” Wu said. “By looking at the exact mutations that occur on the cancer genome, we can estimate how much risk has been due to certain extrinsic factors.”
Lastly, the researchers used computational modeling to determine the contribution of intrinsic processes in the development of cancer. Through probabilistic models, Wu found that DNA replication errors could only theoretically account for about 20 percent of cancer occurrences.
“From these four different methods, our main conclusion is that for most cancers intrinsic risk factors contribute only moderately, about ten to thirty percent of risk,” Wu said. “Correspondingly, 70 to 90 percent can be attributed to extrinsic risk factors.”
