Canadian Cancer Society's commentary regarding new research suggesting cancer is caused by bad luck

01 January 2015

Toronto -

A recent study published in the prestigious journal Science entitled “Variation in cancer risk among tissues can be explained by the number of stem cell divisions” by Dr Tomasetti and Dr Vogelstein from Johns Hopkins investigated why cancers arise more frequently in certain tissues. The study has garnered attention from the scientific community as well as in the media, in part because the authors concluded that two-thirds of the variation in cancer risk among tissues was attributable to “bad luck.”

About the study

The researchers asked why cancers arose more often in some tissues (e.g. in the colon) rather than others (e.g the brain). They focused on stem cells which have distinct abilities to develop into all of the different cell types in the body, replicate themselves and repair damaged tissues. They correlated what was already known about stem cell division rates and determined how they related to the overall rates of cancer in those tissues. This important study demonstrates a previously unknown correlation between the incidence of some cancers and the activity of stem cells.

Why is the study important?

This study integrates different sources of information into a simple model that relates cancer incidence with stem cell division rates in different tissues. Recent work led by Dr John Dick and others has focused on where cancers first start, and what cells they originate in. Consistent with other published work, this new study points to the critical role that stem cells can play in early cancer initiation events and how mutations that occur when they divide their DNA can lead to cancer. It highlights the importance of understanding the fundamental biology of cell mechanisms that contribute to cancer such as cell division, DNA replication, DNA repair, and other biological processes that regulate how cells grow, move and die in the body. Understanding what goes wrong with these processes in cancer provides important targets for new therapies and detection strategies.

What do these findings mean for cancer prevention?

Some reports are interpreting this study to mean that there is little people can do to reduce their risk of developing cancer. In fact, the authors themselves recognize the importance of a number of factors that increase the risk of cancer, such as smoking, alcohol use, ultraviolet light and human papilloma virus infection. There is also a substantial amount of published research using animals, human cells and human populations that definitively shows that certain exposures and behaviours increase the risk of getting cancer, and that a large proportion of cancers could be prevented.  This study points to an interesting area of investigation regarding how different exposures and modifiable factors could influence stem cell behavior as it relates to cancer initiation. 

When we look at all different cancers types, and different types of studies, research has shown that about half of all cancers can be prevented through healthy living and healthy public policies.  The Canadian Cancer Society encourages Canadians to lower their risk of cancer by not smoking, eating well, being active, sitting less, maintaining a healthy body weight, limiting alcohol, being safe in the sun and avoiding indoor tanning.

This study does remind us that a significant proportion of cancers arise from genetic events that cannot be prevented. Understanding their nature and how they arise supports the development of new therapies and ways to detect cancers earlier that will improve outcomes for people affected by cancer.

Some considerations

Cancer is made up of more than 200 different diseases, and many more subtypes of each type of cancer. As this study focused on 31 different tissue types and subtypes of cancer it will be interesting to determine how these findings relate to other cancer types and how broadly they can be applied.  This study doesn’t include two of the most common types of cancer - breast and prostate - as the researchers could not identify reliable stem cell division rates for those tissues.

For this study the researchers had to make certain assumptions about stem cells in different tissues, and noted that their model could be improved if more precise stem cell division rates were available.  Additional confirmation of the underlying characteristics of these stem cell populations in the different tissues studied is likely the most significant aspect of the study that merits further consideration.

In summary

This is an important study that improves our understanding of cancer initiation and biology. As the leading national charitable funder of cancer research in Canada, the Canadian Cancer Society welcomes new knowledge that informs, and sometimes challenges, what we know about cancer.  The Canadian Cancer Society is interested in the results of this high profile study that contribute to our understanding of cancer and wants Canadians to understand these findings in the context of the current state of knowledge. 

Additional information
  • The researchers leading this study developed a statistical model that found a strong correlation between the lifetime incidence of cancer and the number of estimated normal stem cell divisions in specific tissues.  In other words, the greater the number of stem cell divisions, the more likely it was for an error in DNA replication to occur that could lead to cancer.  The researchers concluded that two-thirds of the 31 cancer types (and sub-types) studied arose from random mutations, rather than modifications resulting from, for example, lifestyle or environmental causes.
  • Cancers can arise due to a combination of genetic, environmental, and modifiable lifestyle factors.   While genetic factors could include inherited cancer-promoting genes being passed on through families, most cancers are caused by “sporadic mutations” or genetic changes that are acquired sometime during a person’s lifetime and are not inherited.  Sometimes these mutations are errors that occur during cell division, but can also be caused by factors that damage a cell’s DNA, such as smoking, exposure to certain chemicals and radiation. The risk of sporadic mutations increases with age.
  • Stem cells (that were the focus of this study) were first discovered by Dr Ernest McCullough and Dr James Till at the University of Toronto.  Stem cells have the ability to develop into all of the different cell types in the body, can replicate themselves and repair damaged tissues.  There are different types of stem cells depending on their properties, and there is varying information about the stem cell populations in different tissues.   The Canadian Cancer Society has (and continues) to fund many world-leaders in stem cell research.  Last year the Canadian Cancer Society invested close to $1M in Canadian scientists leading stem cell research projects.