Johns Hopkins Kimmel Cancer Center scientists Bert vogelstein and Cristian Tomasetti made headlines early this year with a paper in Science that measures the variation in cancer risk—across 31 tissue types—that can be explained by random mutations that occur when stem cells divide during an average individual’s lifetime.

Their conclusion? Some two-thirds of the variation in cancer risk across tissues can be explained by “bad luck,” when these random mutations occur in genes that can drive cancer growth.

“This study shows that you can add to your risk of getting cancers by smoking or other poor lifestyle factors,” says Vogelstein, co-director of the Ludwig Center at Johns Hopkins. “However, many forms of cancer are due largely to the bad luck of acquiring a mutation in a cancer driver gene regardless of lifestyle and heredity factors. The best way to eradicate these cancers will be through early detection, when they are still curable by surgery.”

To illustrate their findings, Vogelstein and Tomasetti compare getting cancer to getting into a car accident.

“Our results would be equivalent to showing a high correlation between the length of trip and getting into an accident. Regardless of the destination, the longer the trip is, the higher the risk of an accident,” they note.

1. The mechanical condition of the car is equivalent to inherited genetic mutations. The number of problems in the car—bad brakes, worn tires —increases the risk of an accident.

2. The road conditions on the way to the destination could be likened to the environmental factors in cancer. Worse conditions —slippery roads, poor visibility, dangerous curves—would be associated with a higher risk of an accident.

3. An extremely short trip has a risk close to zero. Regardless of road and car conditions, the probability of an accident occurring increases with distance traveled.

4. Vogelstein and Tomasetti estimate that two-thirds of the variation in the risk of getting into an accident, i.e., developing cancer, is attributable to the length of the trip, i.e., the random mutations that occur in stem cell divisions throughout a person’s lifetime—“bad luck.”

5. Among the cancer types that appear to be explained by “bad luck” along the roadway are childhood cancers and osteosarcomas, brain cancers, and leukemias.

6. Among the cancer types that can be explained by bad luck plus environmental and genetic factors are: 
   
   Basal cell carcinoma, HPV-16 head and neck, thyroid follicular, lung (smokers), colorectal (adenocarcinoma), Lynch colorectal, FAP (colorectal) and HCV hepatocellular.

7. The scientists note that some cancers, such as breast and prostate cancer, were not included in the report because of their inability to find reliable stem cell division rates in the scientific literature.