An ecological approach to understanding differential cancer susceptibility in organs

Cell Press

Why is there a large difference in susceptibility to cancer among the different body organs? Why, for instance, is it rare to find cancer in the small bowel and heart, but common in the colon and breast? And why, although it often produces benign fibroid tumors, is cancer in the uterus a fairly rare event? A number of extrinsic and intrinsic factors have been proposed to explain these anomalies, such as the fact that some organs have higher rates of cellular division than others and so by the laws of chance should accumulate more mutations. Or some organs, like the lungs and the liver, are more susceptible to environmental burdens like tobacco smoke and alcohol. But in a recent paper in Trends in Cancer, “Evolutionary Ecology of Organs: A Missing Link in Cancer Development?” Frederic Thomas, Randy Nesse, Bob Gatenby, together with several other authors including Beata Ujvari, ask us to consider organs as distinct but connected ecosystems whose different vulnerabilities to malignant transformation may be partially explained by how essential each organ is for survival through the age of reproduction.

For instance, they argue, selection for mechanisms to suppress cancer will be greatest in organs that are relatively small and can, therefore, be compromised by even small tumors or are critical for survival and reproduction, such as the heart, brain, and uterus (i.e., keystone organs). While organs that are large or paired, and thus can maintain function even when a relatively large tumor is present, will be less subject to anticancer selection forces. Variation in cancer risk across human organs, they say, may be analogous to ‘Peto’s paradox’: an observed lack of correlation between cancer risk and body mass (and life span) across the animal kingdom. In the same way that long-lived massive animals, like elephants, do not suffer inordinately from cancer thanks to multiple copies of the p53 “guardian of the genome” gene, tissues with high levels of turnover, like the small intestine, which rejuvenates its lining every 5 days, may have evolved especially powerful anticancer mechanisms.

Can a systems ecology approach that applies systems theory to the correlation between the ecosystems of organs and oncogenesis, be a powerful heuristic that could allow us to understand differential oncogenesis in organs more successfully?