Thursday, March 12, 2015

Cancer: Equal Opportunity for All

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).


  1. As Sarah points out, this blog post is a bit disheartening! However, her critical assessment of the study in regards to the future of cancer research and possible prevention is more hopeful. Before reading this blog post, I had a general knowledge that cancer results from random mutations, but I never thought about how difficult these mutations may be to predict, and certainly did not know that 2/3 of cancer cases can be attributed to random chance. The idea of screening patients for mutations in stem cells where certain cancer types are more likely to develop seems to be a promising preventative measure. I would be interested to know if the article mentioned where these stem cells are likely to be located. From previous reading and prevalence of different cancers, I would predict that the colon and breasts in females would be sites of more cell division and possible mutations.

  2. You were right Mae in saying that breast and colon cancers are more common. The researchers found that the same mutation that would theoretically cause cancer in the small intestine or the colon actually resulted in colon cancer at over 100 times the frequency. They also found that colon cells had a much more rapid rate of stem cell division, correlating to the higher rates of cancer in that area even though it shares a mutation with small intestine cancer. This finding along with the high rate of cell division/change in the breast tissue supports their hypothesis that many cancer causing mutations arise simply because certain tissues divide more frequently.

  3. I am not sure that from just these statistics make me believe that cancer is just a random event. It may seem like a random event at the time, but things in the past or the lifestyle choices you have made will certainly effect your body in the future. While this post is rather scary in saying that cancer is just random and you can't attribute it to anything, it makes me think about how many carcinogens we injest through our food and breathe in the air that we have no way of measuring or quantifying. I wonder how many of these "random" mutations really are not random at all. I think it is very possible that we just do not have the propper technology or methods to evaluate them at this point.

  4. It is scary to think that 2/3s of cancer cases come down to random chance. We fret so much about trying to avoid things that cause cancer, from cigarettes to Splenda, but even on our best behavior, making our best efforts to be healthy, it is still very possible we could just randomly get cancer. If it really is the case that 2/3s of cancer is caused by random chance, then I agree with Sarah that screening and catching it early, as well as developing new more effective cancer treatments, might be the best way to deal with this lethal foe.