Hypothetical effects on cancer risk of one or more of three biological levels: The Organism, Within-Organism, and The Genome. Specific abiotic and biotic environment variables (including lifestyle behaviours) will alter one or more of these biological levels and in so doing, increase cancer beyond baseline risks associated with environments experienced over evolutionary time (‘native’ environments). Image courtesy Michael Hochberg.

The vast majority of cancer research focuses on how tumors form in cell cultures and special strains of laboratory mice. But cancer is a larger-scale phenomenon. It’s subject to evolutionary biology, it occurs over a wide range of animal species, and it’s impacted by environmental factors. The complexity of how evolution and environments interact to produce cancer risk is the subject of a new study published in the February issue of Ecology Letters.

The authors of this study, Santa Fe Institute External Professor Michael Hochberg and Robert Noble, both based at the University of Montpellier, France, propose that cancer risk can be partitioned into three interacting causes: the number of stem cell divisions in a body, change in cellular function, and heritable transformations to the cancer phenotype. Importantly, these three phenomena interact in a complex casual web, which itself is influenced by exogenous environments, including lifestyle behaviors, mutagenic exposure, and parasitic infections.

One of the major challenges in understanding the multi-scale nature of cancers is to untangle this intricate, causal network of interactions, says Hochberg. The literature on the subject indicates that novel environments—that is, conditions that significantly differ from those to which most species have evolved and are adapted to—drive the majority of cancers observed in humans and across the tree of life. According to Hochberg, any species showing greater than about 5 percent lifetime risk of cancer is likely, if not certain, to be impacted by novel environments.

Hochberg and Noble evaluated this hypothesis through a demographic model for the human population, and specifically, our hunter-gatherer ancestors. The authors estimate that due to shorter life expectancy, smaller body sizes, and less mutagenic exposure, that pre-modern hunter-gatherers would have had less than a 10 percent chance of getting cancer over their lives (compared to about 40 percent in current first-world countries).

These results require further investigation. The “low hanging fruit,” according to Hochberg, is to develop a first-principles theory to explain how natural selection limits cancer risk across the tree of life, and to understand how sensitivity to the disease may itself be an adaptation to environmental conditions.

Read the paper in Ecology Letters (February 2017)