Are most cancers caused by bad luck?

There has been a recent spate of articles in the popular press (e.g. Telegraph) describing new research purportedly demonstrating that two-thirds of cancers are caused by "bad luck" rather than lifestyle choices or genetics. This finding seems to contradict numerous earlier studies that assert that healthy lifestyle choices can substantially decrease cancer risk (e.g. Guardian). The original research and the interpretation of its findings by the various news outlets require more careful examination.

In the new study, the authors set out to explain the wide variation in cancer risk for different organs (tissue types). For example, the risk of bone cancer is 100 times less than the risk of colorectal cancer (Figure 1). They focused on the stems cells of each tissue and estimated the total number of cell divisions that these stem cells undergo during a lifetime.  Remarkably there was a striking correlation between the "total number of stem cell divisions" and the "lifetime risk of cancer" in a given tissue i.e. those tissues that undergo more stem cell divisions are more likely to give rise to cancer (Figure 1). The explanation is that each stem cell division increases the chance that the stem cell may mutate (during replication) and that the mutations could be tumorigenic. The more random "hits" (mutations) that a stem cell endures, the more likely that it will transform into a cancer cell.

Figure 1. The relationship between the total number of stem cell divisions in the lifetime of a tissue versus the lifetime risk of cancer in that tissue (from Tomasetti and Vogelstein, Science).

One critique of this work is that correlation does not imply causation, and so that the correlated variable "total number of stem cell divisions" and the presumed random mutations in the stem cells may not cause the cancer in a tissue despite the excellent correlation. Demonstrating a causal relationship requires independent evidence that reveals details about the mechanism which is lacking at the moment. Yet without a doubt the correlation is suggestive.

The second more important issue is that the popular press misrepresented the findings in a fundamental way. Assuming that the correlation does indeed imply a causal relationship between the total number of stem cells division and the lifetime risk of cancer in a tissue, this result explains the variance in cancer risk among tissues not the variance in cancer risk among people. Random chance may play a significant role in determining why you get colorectal cancer instead of bone cancer, but it may not play that same significant role in determining why one person gets colorectal cancer and another doesn't.

So are most cancers caused by bad luck?

We don't know.

Most cancers are caused by a combination of genetics, environment and lifestyle choices, and bad luck. The relative weighting of each of these causes depends on the cancer and on the individual. For certain cancers, the genetics are important. For example, the BRCA1 mutation (e.g. the mutation that Ms Angelina Jolie possesses) greatly increases the risk of breast cancer.

We do know for many cancers lifestyle choices can be a very significant contributor. The classic example is lung cancer. Smoking increases your chance of lung cancer by 15 to 30-fold. That is huge.

This is a complex issue that will require further research to resolve. Of course, chance plays some role in cancer. However, the safest bet (Figure 2) is to minimize your risk (and bad luck) by performing the appropriate cancer diagnostics (e.g. colonoscopy) and to lead a healthy lifestyle.

Figure 2. Bad luck plays a role in cancer but you want to minimize this risk by making healthy lifestyle choices.