Abstract
Tomasetti and Vogelstein (2015a) find that the incidence of a set of cancer types is correlated with the total number of normal stem cell divisions. Here, we separate the effects of standing stem cell number (i.e., organ or tissue size) and per stem cell lifetime replication rate. We show that each has a statistically significant and independent effect on explaining variation in cancer incidence over the 31 cases considered by Tomasetti and Vogelstein. When considering the total number of stem cell divisions and when removing cases associated with disease or carcinogens, we find that cancer incidence attains a plateau of approximately 0.6% incidence for the cases considered by these authors. We further demonstrate that grouping by anatomical site explains most of the remaining variation in risk between cancer types. This new analysis suggests that cancer risk depends not only on the number of stem cell divisions but varies enormously ($\sim$10,000 times) depending on the stem cell's environment. Future research should investigate how tissue characteristics (anatomical site, type, size, stem cell divisions) explain cancer incidence over a wider range of cancers, to what extent different tissues express specific protective mechanisms, and whether any differential protection can be attributed to natural selection.