If every living cell had an equal chance of becoming cancerous, whales and elephants should have a greater risk of developing cancer than do humans or mice. But across species, the occurrence of cancer does not show a correlation with body mass. According to a new model, the paradox could be explained if animals were striking a balance between reducing cancer risk and other priorities, such as maximising the number of offspring.
The lack of correlation between body mass and cancer risk is known as Peto’s paradox, after epidemiologist Richard Peto of Oxford University in the UK, who noted it in the 1970s. Evolutionary biologists think that it results from larger animals using protective mechanisms that many smaller animals do not.
In an attempt to identify how greater body mass might foster such mechanisms, evolutionary biologist Benjamin Roche at the Institute of Research for Development in Montpellier, France, and his colleagues created a theoretical model to simulate which of 100 possible genetic-mutation strategies would become most prevalent over 4,000 generations.
The model included two gene types: proto-oncogenes, which can cause normal cells to become cancerous, and tumour-suppressor genes, which repair cellular damage that could otherwise lead to cancer. For carcinogenesis to occur, the team assumed that proto-oncogenes must be activated and tumour-suppressor genes must be rendered inactive.
“We found that tumour-suppressor genes and proto-oncogenes react differently along a gradient of body masses,” says Roche. “Their evolutionary dynamics are linked.” Proto-oncogene activation decreased steadily with increasing body mass, the team found.