Cristian Tomasetti and Bert Vogelstein
Most cells in tissues are partially or fully differentiated, typically short-lived and unlikely to be able to initiate a tumour. However, stem cells have the capacity to self-renew and can be involved in tumourigenesis. It is well known that environmental factors, such as carcinogens, can increase cancer risk; but also that different tissues are intrinsically more predisposed to neoplastic transformation than others. The authors investigate which of these factors explains lifetime cancer risk.
They find that the total number of stem cell differentiations in a particular tissue, correlates strongly (0.804) with the lifetime risk of cancer in that tissue. They calculate that 65% (39% to 81%; 95% CI) of the variance in cancer risk can be attributed to the total number of stem cell divisions in the tissue. The authors propose classifying cancers into two categories: deterministic tumours (D-tumours) which are heavily influenced by the environment, and replicative tumours (R-tumours) which are driven by mainly stochastic factors. They use unsupervised clustering to find that most are R-tumours.