One question has intrigued cancer researchers for decades: why are some tissues more susceptible to developing cancers than others? Genetic and lifestyle factors have been frequently cited as common culprits, but they far from explain this phenomenon. In a report published in Science last week, Cristian Tomasetti and Bert Vogelstein show that the number of stem cell divisions may explain differences in the relative risk of cancer among tissues.
A person’s lifetime risk of being diagnosed with cancer is 11.5 times higher in the lung than in the brain. Such differences have been attributed to genetic or environmental factors, but neither can explain fully the differences in cancer risk between different tissue types. For example, cells of the airways that are equally bombarded with mutagens from cigarette smoke do not develop cancer at the same rate.
According to the somatic mutation theory, cancer is caused by the accumulation of genetic changes in the same cell. Because mistakes in copying DNA sometimes occur during cell division, it was reasoned many years ago that the number of cells in a tissue and their cumulative number of divisions should be related to cancer risk. But most differentiated cells are short-lived and cannot seed a tumor. Stem cells on the other hand self-renew and give rise to clonal populations of cells within tissues.
Tomasetti and Vogelstein thus had a simple but brilliant idea: they identified 31 tissue types for which the number and dynamics of stem cell divisions are known, and plotted the number of stem cell divisions against the relative risk of cancer for each tissue. Here’s what their graph shows:
- There is a strong positive correlation between the number of stem cell divisions in a given tissue and the life time risk of cancer for that tissue.
- This correlation extends across five orders of magnitude, and thus applies to cancers with an enormous difference in incidence.
- Approximately 65% of differences in cancer risk between tissues can be explained by the number of stem cell divisions.
Thus, it appears that the roll of the dice, or in this case random errors in the unravelling and copying of chromosomes, are the main reason for differences in cancer risk among tissues.
Check out the full report in Science, January 2015