Although it’s easy to misinterpret these findings, the authors noted that “we are not assessing the proportion of cancers explained” by random mutations, but the proportion of mutations that are random — a distinction that’s easy to miss despite its importance, according to lead author Cristian Tomasetti, MD, PhD, assistant professor of biostatistics at the Kimmel Cancer Center and the Johns Hopkins Bloomberg School of Public Health.
Because of the “2-hit hypothesis,” it’s possible that individuals born with 1 hereditary mutation will not develop cancer if they do not acquire a second mutation through environmental exposure or a random error.
“You can have a mutation in 1 of the pairs of chromosomes, but the second 1 is necessary for cancer development. You can modify your environmental risk, but you can’t at this time modify your DNA replication risk,” said Dr Chow. He added that random errors due to reactive oxygen species, for example, may be minimized through reduction of systemic inflammation. Prevention efforts and early detection are therefore still critically important.
“We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations,” said co-author Bert Vogelstein, MD, co-director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center, adding that “better methods to detect all cancers earlier, while they are still curable, are urgently needed.”
According to Dr Chow, these data “are a call to increase cancer screening and detection at a very early stage of cancer. These errors are unavoidable now, but may be avoidable in the future. For now, the best thing we can do is to catch it early.”
- Tomasetti C, Vogelstein B. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science. 2015;347:78-81.
- Tomasetti C, Li L, Vogelstein B. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science. 2017;355:1330-4.