Risk of getting cancer more than just bad luck

Utrecht, October 4, 2016 – Scientists at the University Medical Center (UMC) Utrecht and the Hubrecht Institute have managed to detect errors in the DNA code of healthy human stem cells for the first time. They found that stem cells in organs with a high cancer risk collect the same amount of DNA–errors as organs with a low cancer risk. This surprising finding shows that the probability of cancer cannot be explained by the number of DNA–errors. The study is published in Nature this week.

Some types of cancer happen more often than others. Organs with slow stem cells division show a lower risk of cancer. For example, colorectal cancer occurs 15 times more often than liver cancer. Stem cells are the main source for the renewal of our organs. The presumption was that the difference in cancer risk could be explained by the number of unavoidable DNA errors that accumulate during the division of stem cells. Cells that divide more often, would unfortunately contain more DNA-errors and cause cancer sooner. On this controversial idea was published last year, which is currently debated fiercely in the scientific community. New DNA-research shows that every stem cell receives 40 DNA-errors every year, regardless of the cell division rate.

Bad luck or lifestyle?
Lifestyle can contribute to cancer: smoking significantly increases the risk of lung cancer. For most organs, however, it is unknown to what extent the risk of cancer is the result of bad luck or unhealthy lifestyle. The current study contributes to a better understanding of the role of DNA-errors in the development of cancer and may contribute to better prevention in the future.

Scientist Dr. Ruben van Boxtel, “We were surprised to see that the amount of DNA errors in stem cells is the same for different organs. This suggests, at least for some organs, that the risk of cancer is not simply due to a difference in the quantity of accumulated DNA errors. ”

Organoids
This international study has used a unique combination of cultured miniature organs (organoids) and large-scale DNA analysis. These have been developed in the labs of Professor. Hans Clevers of the Hubrecht Institute and prof. Edwin Cuppen of the UMC Utrecht. The scientists have mapped the full genetic profile of these organoids. Thereby they examined the DNA from colon, small intestine and liver cultures, derived from stem cells of people aged between 3 and 87 years old.

Publication
Blokzijl F. et al. Tissue-specific mutation accumulation in human adult stem cells during life. Nature 2016 doi:10.1038/nature19768