Strategies to Prevent "Bad Luck" in Cancer

Abstract

It is impossible to predict exactly who will develop a cancer and who will not. We know that several "risk factors" may increase the chance of getting cancer and that risk increases with age. However, even with that in mind we seem to be able to explain only a certain number of cancers. Recently, Tomasetti and Vogelstein published a provocative article in Science stating that a large percentage of cancers may be due to "bad luck" (stochastic mutation events during DNA replication) and only a few to carcinogens, pathogens, or inherited genes and that this should impact public health policies. However, their intriguing analysis has numerous limitations, some of which have already been commented upon, including the likely biased subset of cancers and that finding a correlation does not signify a cause-effect mechanism. Here, we point out that there may also be an alternative explanation for the data, the cancer stem cell hypothesis, which postulates that cancers are derived from tissue stem cells and not from somatic differentiated cells. We also highlight the importance of the tissue microenvironment in the growth of transformed cells and outline a table of concurrent factors for several cancers. The message communicated to the public should not be one of helplessness in avoiding cancers, particularly given the now extensive knowledge of known risk factors and several agents/behaviors that can lower risk for specific cancers. While some tumors will still be due to chance, prevention should still be a primary goal for public health policies.

Figure 1.

Log-log plot of the stem cell number within a specific tissue (adapted from Supplementary Table 1 of [1]) and the calculated cancer risk for that tissue. There appears to be a correlation between stem cell number within a tissue and the likelihood of developing a cancer in that tissue. The dots in black represent the tumors considered replicative (1); the gray dots indicate those considered deterministic. ADC = adenocarcinoma; AML = acute myeloid leukemia; CLL = chronic lymphocytic leukemia; FAP = familial adenomatous polyposis; HBV = hepatitis B virus; HCV = hepatitis C virus; HNPCC = hereditary non-polyposis colorectal cancer; HPV = human papillomavirus; SCC = squamous cell carcinoma.