Are Most Cancers Caused by Specific Risk Factors Acting on Tissues With High Underlying Stem Cell Divisions?

Abstract

A recent paper by Tomasetti and Vogelstein demonstrated a high correlation coefficient of 0.81 between estimated lifetime normal renewing cell (stem cell) divisions among tissues in the body and the lifetime cancer risk in that organ. This finding has been interpreted frequently to suggest that if two-thirds of cancers arise primarily through normal proliferation then environmental and hereditary factors combined could explain only one-third of cancers. Yet, the pool of dividing stem cells is what risk factors act upon; it is unlikely that risk factors and proliferation act completely independently and are simply additive; thus, there is no constraint that stem cell proliferation and environmental/genetic attributable risk sum to 100%. The cancers illustrated to represent lifetime risk in the paper by Tomasetti and Vogelstein all implicitly incorporate risk factors common in the United States (example, obesity, physical inactivity, tobacco, alcohol, diet, infectious agents). In fact, there is little evidence that a cancer would exceed a substantial rate, such as greater than 1% lifetime risk, in the absence of an important risk factor. Relatively high rates of cancer (eg, > 1% lifetime risk) only seem to occur in organs when strong risk factors (example, 10- to 20-fold) are superimposed on relatively high stem cell division. In organs with low stem cell divisions, the lifetime cancer risk will typically be very low. The major types and most abundant cancers in a given population will arise from tissues that have relatively high stem cell division rates and that have a high prevalence of strong relevant risk factors.