CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Editor: Deborah Sesok-Pizzini, MD, MBA, professor, Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, and chief, Division of Transfusion Medicine, Children’s Hospital of Philadelphia.
Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention
Cancers are caused by mutations that may be inherited or induced by environmental factors or that may result from DNA replication errors. The mutations due to random mistakes made during normal DNA replication may explain why cancers occur much more commonly in some tissues than others. Approximately three mutations occur every time a normal human stem cell divides. The authors of this study proposed that mutations resulting from DNA replication errors play a major role in cancer development. They studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries worldwide that represented a variety of environments. They had previously studied just the U.S. population, assuming that the environmental conditions to which study participants were exposed were more uniform. In the current study, the authors analyzed data from 423 cancer registries that were made available by the International Agency for Research on Cancer. For each country, they calculated the correlation between the number of stem cell divisions in 17 different tissues and the lifetime incidence of cancer in those tissues. The results showed a strong correlation between cancer incidence and normal stem cell division in subjects in all countries, regardless of environment. The conclusions were supported by an independent approach based on cancer genome sequencing and epidemiological data, which suggested that the mutations resulting from DNA replication errors were responsible for two-thirds of the mutations in human cancers. The authors concluded that this study accentuates the importance of early detection and intervention to reduce deaths from many cancers that arise from unavoidable DNA replication errors. They also noted that this study provides a well-defined molecular explanation for the large and unpreventable component of cancer risk that has long puzzled epidemiologists.
Tomasetti C, Li L, Vogelstein B. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science. 2017;355:1330–1334.
Correspondence: Cristian Tomasetti at ctomasetti@jhu.edu or Dr. Bert Vogelstein at vogelbe@jhmi.edu