Scientists from the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center have created a statistical model that measures how many cancer cases are caused mainly by random mutations, or changes, that occur when cells divide.
Their study, published today in Science, shows that two-thirds of adult cancers across different tissues are the result of “bad luck,” or random mutations that occur in genes that can drive cancer growth. The remaining one third of adult cancer cases are caused by environmental factors and inherited genes, according to the researchers.
Scientists know that cancer can develop when tissue-specific stem cells make random mistakes, causing one chemical letter in DNA to be incorrectly swapped for another during cell division and replication.
“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,” said Dr. Bert Vogelstein, a Clayton professor of oncology at the Johns Hopkins University School of Medicine.
22 Cancers Are Driven by ‘Bad Luck’
Vogelstein and Christian Tomasetti, Ph.D., an assistant professor of oncology at Johns Hopkins, first charted the number of stem cell divisions in 31 types of tissue. They compared these rates with the lifetime risk of cancer in the same tissues among Americans.
The correlation between the total number of stem cell divisions and cancer risk was shown to be 0.804. Mathematically, the closer this value is to one, the more closely stem cell divisions and cancer risk are linked.
The researchers calculated which cancer types had an incidence predicted by the number of stem cell divisions and which had a higher incidence that could not be explained by random mutations alone. They found that 22 types of cancer could be largely explained by the “bad luck” factor of random DNA changes.
The remaining nine cancer types had incidences higher than would be expected in the case of simple "bad luck." These cancers were caused by a combination of poor luck plus environmental or inherited factors, the scientists concluded.
“We found that the types of cancer that had higher risk than predicted by the number of stem cell divisions were precisely the ones you’d expect, including lung cancer, which is linked to smoking; skin cancer, linked to sun exposure; and forms of cancers associated with hereditary syndromes,” said Vogelstein.
Breast and prostate cancer were not included in the study because the researchers could not find reliable stem cell division rates for these tissues in the scientific literature.
Poor Lifestyle Choices Don’t Help
Vogelstein explained that colon tissue undergoes four times more stem cell divisions than small intestinal tissue in humans. So as you would expect, colon cancer is much more common than small intestinal cancer. The colon is also exposed to more environmental factors than the small intestine.
However, the researchers found that mice had fewer stem cell divisions in their colon tissue than in their small intestinal tissue. So in mice, cancer incidence is lower in the colon than in the small intestine.
This new study shows that most people who are exposed to cancer-causing agents such as tobacco, but who are cancer free for a long time, simply have good luck rather than good genes. But poor lifestyle choices can add to this “bad luck” factor, said Vogelstein.
“With two-thirds of cancer incidence across tissues 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,” said Tomasetti in a press statement.
Tomasetti said that we need to devote more resources to detecting such cancers in the early stages when there is a better chance of a cure.