Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention.
Level 4 - case-series / case-control
Ecological correlation and mathematical modeling using aggregate epidemiological and genomic data (by design analogy).
PubMed 28336671 · doi:10.1126/science.aaf9011
What was done
The authors analyzed the relationship between the estimated number of normal stem cell divisions across tissues and the risk of 17 cancer types across 69 countries. An independent analytical approach combining cancer genome sequencing and epidemiological data was also used to estimate the proportion of cancer mutations attributable to random DNA replication errors.
What was found
Across all 69 countries, cancer incidence strongly correlated with normal stem cell divisions regardless of environmental differences, showing a median correlation coefficient of 0.80. Genome sequencing and epidemiological data modeling indicated that random DNA replication errors account for two-thirds of the mutations in human cancers.
Why it matters
This work demonstrates that a major fraction of human cancer mutations arises from unavoidable biological replication errors, emphasizing the essential role of early detection and intervention in addition to primary environmental cancer prevention.
Limits
The study relies on aggregate ecological and cross-country correlations rather than individual-level longitudinal tracking. Specific sample sizes for genomic datasets and confidence intervals are not reported in the abstract.
Cited by
- supports Cancer incidence increases with age primarily because dividing cells accumulate mutations and DNA damage over time.