Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention.
Cancers are caused by mutations that may be inherited, induced by environmental factors, or result from DNA replication errors (R). We studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries throughout the world. The data revealed a strong correlation (median = 0.80) between cancer incidence and normal stem cell divisions in all countries, regardless of their environment. The major role of R mutations in cancer etiology was supported by an independent approach, based solely on cancer genome sequencing and epidemiological data, which suggested that R mutations are responsible for two-thirds of the mutations in human cancers. All of these results are consistent with epidemiological estimates of the fraction of cancers that can be prevented by changes in the environment. Moreover, they accentuate the importance of early detection and intervention to reduce deaths from the many cancers arising from unavoidable R mutations.
Division of Biostatistics and Bioinformatics, Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 550 North Broadway, Baltimore, MD 21205, USA. ctomasetti@jhu.edu vogelbe@jhmi.edu.|Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Cristian
0000-0003-3277-4804
C
Tomasetti
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Lu
0000-0002-1920-4965
L
Li
Ludwig Center and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, 1650 Orleans Street, Baltimore, MD 21205, USA. ctomasetti@jhu.edu vogelbe@jhmi.edu.
Bert
0000-0003-0766-3854
B
Vogelstein
D000349:Africa / Q000453:epidemiology; D001208:Asia / Q000453:epidemiology; D017691:Caribbean Region / Q000453:epidemiology; D002455:Cell Division; D004261:DNA Replication / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D015994:Incidence; D007843:Latin America / Q000453:epidemiology; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control*; D009656:North America / Q000453:epidemiology; D044349:Oceania / Q000453:epidemiology; D011322:Primary Prevention; D013234:Stem Cells / Q000166:cytology*