Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions.
Level 4 - case-series / case-control
Cross-sectional ecological correlation study across tissue types (by design analogy, not clinical CEBM)
PubMed 25554788 · doi:10.1126/science.1260825
What was done
Analyzed the relationship between the lifetime risk of various human cancer types and the total number of normal self-renewing stem cell divisions maintaining homeostasis across different tissue types.
What was found
Lifetime risk across many different cancer types was strongly correlated (correlation coefficient = 0.81) with the total number of divisions of normal self-renewing cells maintaining tissue homeostasis. Based on this, the authors state that only a third of variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions, with the remainder attributable to random replicative mutations.
Why it matters
It offers a quantitative model explaining why baseline cancer risk varies drastically across different human organs, pointing to intrinsic stem cell replication rates as a primary driver of tissue-specific variation.
Limits
The abstract does not specify the exact sample size (number of tissue/cancer types evaluated), confidence intervals, or specific datasets used. As an aggregate ecological correlation, it describes inter-tissue variation rather than individual-level etiology or causality.
Cited by
- supports Cancer incidence increases with age primarily because dividing cells accumulate mutations and DNA damage over time.