“Bad luck” of random mutations plays predominant role in cancer, study shows

Scientists from the Johns Hopkins Kimmel Cancer Center have created 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. By their measure, 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.

In a report on the statistical findings, published recently in Science, researchers say they 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. Stem cells “self-renew,” thus repopulating cells that die off in a specific organ.

It has been well known that cancer arises when tissue-specific stem cells make random mutations; one chemical letter in DNA is incorrectly swapped for another during the replication process in cell division. The more these mutations accumulate, the higher the risk that cells will grow unchecked, a hallmark of cancer. The actual contribution of these random mistakes to cancer incidence, in comparison to the contribution of hereditary or environmental factors, was not previously known.

To sort out the role of such random mutations in cancer risk, the scientists charted the number of stem cell divisions in 31 tissues and compared these rates with the lifetime risks of cancer in the same tissues among Americans. From this so-called data scatterplot, they determined the correlation between the total number of stem cell divisions and cancer risk to be 0.804. Mathematically, the closer this value is to one, the more stem cell divisions and cancer risk are correlated.

Finally, the researchers classified the types of cancers they studied into two groups. They statistically calculated which cancer types had an incidence predicted by the number of stem cell divisions and which had higher incidence. They found that 22 cancer types could be largely explained by the “bad luck” factor of random DNA mutations during cell division. The other 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.