Is ‘Bad Luck' an Important Determinant of Cancer Incidence and Does This Concept Apply to Kidney Tumors?

A study recently published in Science demonstrates a strong correlation between the total number of stem cell divisions and the lifetime risk of cancer in various organs. The tumors considered are divided into two classes, that is, D (Deterministic) and R (Replicative). Stochastic factors presumably attributable to errors deriving from DNA replication are proposed to be at the basis of R-tumor frequency, leading to the conclusion that ‘bad luck' is a primary determinant of certain types of cancer. The present Second Opinion highlights potential problems associated with the hypothesis of the study, as some of these also apply to kidney cancer. The aim is to point out that chance is not a major cause of cancer incidence because it is not substantiated by the data available through epidemiological evidence. In particular, we highlight that differences in tumor incidence associated with sex and geographic areas are not in line with the ‘bad luck' hypothesis. Further aspects of tumor biology that do not entirely fit with the idea that stochastic events related to DNA replication of normal stem cells are the heterogeneity of the cancer cell phenotype and the heterogeneity of intra-organ localization, often observed in tumors originating from the same tissue. From a public health perspective, the points discussed here as well as the absence of data on prevalent tumors, like breast and prostate cancer, do not support the oversimplified message conveyed by the media that the majority of cancer cases cannot be prevented.