Knowing the origins of cancer help to understand how it can be treated, and in some cases, how it can be prevented. We know cancer can be caused by exposure to harmful environments or by genes gone haywire. However, only an estimated 5-10% of cancers have been found to have genetic components. This would leave the other 90% of cancer risk to be attributed to the outside world. But, cancer seems to develop in places that we do not expect, where there is less exposure to the environment, or where there is not a direct genetic link to a greater risk of developing cancer. Why is this?
Tomasetti and Vogelstein think they have figured out why cancer, some of it anyway, develops when we least expect it. Bad luck. The authors found that only one third of cancer risk can be attributed to environmental or genetic factors. The other two thirds, just comes down to bad luck, AKA, random mutations. These mutations happen when a cell is dividing, and instead of going through the natural cell life cycle, it continues to live and duplicate until there is a mass of the same undying cell. So does this mean that all the cells in our body have an equal chance of developing cancer, and that we have two thirds of a chance of getting cancer?
The authors tell us not to fret, that only stem cells are those that can eventually turn into cancerous cells. Stem cells keep our body replenished by dividing and creating new cells when the old ones become worn out, this is how our body renews itself. Over time, their stock is depleted, and this is how someone gets older. When someone has less stem cells or runs out of them, their body cannot replace things that are past their use, leading to aging of they body and eventually death. But these can also develop into cancer cells. Not all these stem cells divide at the same rate though, with some not dividing often, and others doing so frequently. This is where the 66% of cancer risk comes from. By looking at the average number of stem cell divisions in a life time they found a strong correlation between an increased rate of cancer and a larger number of stem cell divisions in a specific tissue. This explained the difference between the rates of certain tissues’ cancers that would be caused by the same malfunctioning gene. One tissue’s stem cells divide more than the other, making it more likely that something will go wrong. And as a person's cells age, they are more likely to have mutations through mistakes in cell division.
Remember though, that they found that one third of cancers are caused by environmental factors or inherited risks. So in order to weed out the cancers which are most likely because of these factors they constructed a variable they called the “extra risk score” (ERS), which was the product of the lifetime risk of cancer of a tissue and its average total number of stem cell divisions. If this number is high, this showed that the risk of that particular type of cancer was high relative to the number of stem cell divisions. So that cancer was more likely to be influenced by environmental and genetic factors. And vice versa, those with low ERS were those cancers whose risk could be attributed to the number of stem cell divisions. Their calculations were in line with many previous studies, which showed environmental and genetic causes for certain cancers that had high ERS in this study.
What do we get out of all these percentages and risk scores? Basically, that for the average person, cancer is just a matter of chance, that a mutation happened in one of their stem cells, and it happened to turn into cancer. This study simply shows us that out of the risk of getting cancer in the first place (which varies based on the type), on average, two thirds of that risk is due to random chance, just bad luck. While this is not exactly reassuring, it still has to be looked at critically. This study gives medical researchers, doctors, a new way to look at treating cancer. If most of cancers are due to random mutations that means that trying to find every random inherited gene that causes cancer will not necessarily be the most effective method. If two thirds of the chance of getting cancer is random, that means that early prevention may be the most lethal weapon (for the cancer). By doing screenings, and checking people for cancers in places that have a higher risk because of the higher rate of stem cell divisions, doctors can work to catch cancer earlier and eradicate it before it becomes life threatening. So even though this study is a bit disheartening, we can look at it hopefully, with an eye on the future of cancer treatment.
Tomasetti, Cristian, and Volgelstein, Bert. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347, 78-81 (2015).
Figure 1. Siegel, Rebecca, Naishadham, Deepa, and Jemal,Ahmedin. Cancer Statistics, 2013. CA Cancer Journal Clinic 63, 11-31 (2013).