Cancer: Just bad luck? Analysis suggests extrinsic causes in 70-90% of cases| Nature

Access to the full content of this site is available only to registered healthcare professionals. Register to read more

Takeaway

  • The analysis found between 70% to 90% of all cancers are caused, not by the bad luck of random mutations, but by behavioral, environmental, and other external factors.

Study design

  • Analysis of cancer risk compared to normal tissue cell division.
  • Analyses of data from the Surveillance, Epidemiologic and End Results (SEER) program.
  • Analysis of mutational signatures in cancer, categorizing them as intrinsic — such as age-associated mutations — and extrinsic — such as mutations associated with carcinogen exposures.
  • Modeling theoretical intrinsic risk looking at potential lifetime cancer risk due to intrinsic processes, based on known mutation rates, and the likelihood those processes would be sufficient for cancer onset.

Key findings

  • Unavoidable intrinsic risk factors, such as random errors in DNA replication contribute only modestly to cancer development (<10%~30%).
  • Rates of endogenous mutation accumulation by intrinsic processes are insufficient to account for observed cancer risk.
  • Although some cancers had 50% intrinsic mutations, m...