Note for: Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention

 Note for: Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention

doi: 10.1126/science.aaf9011

This paper reveals a mutation in cancers, mostly occur from error in replication (2/3) -- theory observes the replication of normal stem cell divisions and relates to cancer incidence in a different country.

Cancer comes from gradual accumulation of driver gene mutations which results from increased cell proliferation.

Factors that contribute to mutation

1. Environment (E)

2. Hereditary (H) -- identify through the genes responsible for cancer predisposition syndrome

3. Random (R) mistake during normal DNA replication -- thus cancer arises more in some tissues

Three mutations occur every time a normal stem cell divides.

Their observation -- number of endogenous mutations ® results from stem cell divisions in a tissue.

Determine 69 countries with a variety of environments throughout the world -- representing 4.8 billion people (2/3 world population).

Using 423 cancer registries -- http://ci5.iarc.fr/CI5-X/Pages/download.aspx

17 different cancer types

Further investigation;

• Too few stem cell divisions to account for cancer incidence

• Looking for a way to prevent the random mistake

• Random mistakes are at least from

• Quantum effects on base pairing

• Mistakes made by polymerases

• Hydrolytic deamination of bases

• Damage by endogenously produced ROS or other metabolites