Random Mutations May Be Leading Cause of Oncogenesis

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According to a study across all 32 cancer types, data suggest that 66% of mutations leading to cancer are the result of random events.
According to a study across all 32 cancer types, data suggest that 66% of mutations leading to cancer are the result of random events.

Researchers from Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, used an analysis of stem cell replication to conclude that across cancer types, approximately 66% of cancer-causing mutations result from random errors in replication.1

Every time cells divide, the potential for a copy error is introduced, so the more often cells divide, the more likely a copy error. Building on research published 2 years ago, which used data from the United States only, the researchers expanded their analysis to include data from 69 countries that represent two-thirds of the world population.2 In their earlier work, the authors found a correlation between stem cell divisions and cancer incidence, though the correlation may have been limited, they wrote in the current article, by the “relatively uniform environmental conditions” found in the United States.

Expanding their work to include data from diverse populations with vastly different histories of environmental exposure around the world, the researchers claimed that the correlation between the incidence of specific cancer types and the rate of stem cell replication remains strong.

To determine the role of random mutations in each cancer type, cancer-causing mutations were categorized as hereditary, environmental, or due to random errors. The mutations were analyzed using a mathematical model based on DNA sequencing data from the Cancer Genome Atlas and epidemiologic data for 32 cancer types from Cancer Research UK.

The proportion due to random mutations varied among cancer types, but across all 32 cancer types the data suggest 66% of mutations leading to cancer are the result of random events. Environmental causes accounted for 29% and heredity for just 5% of cancer-causing mutations. “It's a highly theoretical article, but I think it's on base. At least a third of cancers are due to errors in DNA replication in the stem cells, which at the present time we can't modify,” said Warren Chow, MD, clinical professor in the department of medical oncology at City of Hope National Medical Center in Duarte, California, who was not involved in the study.

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