Random Stem Cells Mutations Plays Predominant Role in Cancer

A statistical model that measures the proportion of cancer incidence, across many tissue types, caused mainly by random mutations that occur when stem cells divide has been developed by scientists from the Johns Hopkins Kimmel Cancer Center. According to their study, two-thirds of adult cancer incidence across tissues can be explained primarily by 'bad luck', when these random mutations occur in genes that can drive cancer growth, while the remaining third are due to environmental factors and inherited genes.

Investigator Dr. Bert Vogelstein said, "All cancers are caused by a combination of bad luck, the environment and heredity, and we've created a model that may help quantify how much of these three factors contribute to cancer development. Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their good genes, but the truth is that most of them simply had good luck."

Cancer arises when tissue-specific stem cells make random mutations, when one chemical letter in DNA is incorrectly swapped for another during the replication process in cell division. The more mutations accumulate, the higher the risk that cells will grow unchecked. The study explains the actual contribution of these random mistakes to cancer incidence, in comparison to the contribution of hereditary or environmental factors.

Researchers came to their conclusions by searching the scientific literature for information on the cumulative total number of divisions of stem cells among 31 tissue types during an average individual's lifetime and compared these rates with the lifetime risks of cancer in the same tissues among Americans. They determined the correlation between the total number of stem cell divisions and cancer risk to be 0.804. Stem cells self-renew, thus re-populating cells that die off in a specific organ. Thus, the more stem cell divisions and cancer risk are correlated.

Biomathematician Cristian Tomasetti said, "If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others. We should focus more resources on finding ways to detect such cancers at early, curable stages," he adds.

The research duo also found that 22 cancer types could be largely explained by the 'bad luck' factor of random DNA mutations during cell division, while nine cancer types had incidences higher than predicted by 'bad luck' and were presumably due to a combination of bad luck plus environmental or inherited factors.

The study is published in 'Science'.

Source: Medindia