[Report] Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention

The claim that sparked this controversy?

Even without an action plan, the question of how much human cancer is caused by bad luck and how much is caused by bad things we do “is super fascinating”, says Martin Nowak, a biologist and mathematician at Harvard who wrote a commentary about the study for Science.

The latest study addresses two criticisms of the 2015 paper.

Published in the journal Science, it can be found online at j.mp/cancermutations.

More commonly, damage is caused by what scientists call environmental factors – the assault on DNA from the world around us and how we live our lives. Epidemiological studies suggest that about 42% of cancers are preventable, he says, and his results do not contradict that. “Most of the time these mutations don’t cause any harm”, said Bert Vogelstein, co-director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center. That report was controversial because it was interpreted as saying that most cancers are the result of “bad luck”. Scientists also said the study sent the wrong message, interfering with efforts to persuade the public to reduce cancer risk factors. “Those who have done what they should, all the preventative measures and still get it, they need to understand that these cancers would have occurred no matter what they did”.

Dr Vogelstein says this research highlights an urgent need for new methods to detect all cancers – the ones that can’t be prevented – earlier while they’re still curable.

Not all critics of the first paper were swayed, however.

The cells in our bodies are constantly moving and changing and each time a cell divides, there is a chance for errors during the DNA replication process, reports Nature.

They found a very close correlation.

The Hopkins team originally used US -based Surveillance, Epidemiology, and End Results (SEER) data on lifetime cancer risk, finding a strong positive, linear correlation between number of stem cell divisions and cancer incidence. “An understanding of cancer risk that did not take bad luck into account would be as inappropriate as one that did not take environmental or hereditary factors into account”, they conclude.

Numerous genetic mutations in tumour cells such as these are created by DNA-replication errors. For instance, the “cause” of the Himalayas is the Indian tectonic plate smashing into the Eurasian Plate. For example, environmental influences such as smoking predominate in lung cancer. In other words, the higher incidence of colon cancer versus brain cancer could be due to the relatively higher number of stem cell divisions in the colon compared to the relative infrequency of these divisions in the brain. That’s what the Hopkins scientists found.

More than two-thirds of cancer mutations are the result of random mistakes in DNA replication that occur when normal cells divide, a new study reveals. Across all cancer types, environment and lifestyle factors, such as smoking and obesity, contribute 29 percent of cancer mutations, and 5 percent are inherited.

“Despite the role of the random replication component in producing mutations, you could still reduce the cancer risk hugely, for many types of cancer, by getting rid of the environmental and/or hereditary causes”, he said. “It’s important to consider the randomness, or bad luck, that comes with cellular division”, he says. If so many cancers arise from mistakes that cells make when they divide, then reducing exposure to cancer-causing compounds such as those in cigarettes or workplace carcinogens won’t help much, they argued. So, avoiding air pollution alone-thus preventing that induced mutation-could prevent the cancer. Several mutations are required for cancer.

With the new study, Tomasetti, Vogelstein, and colleague Lu Li essentially double down on the idea that random mutations play a big role while trying to clear the air a bit.

This time the Hopkins team agrees.

Vogelstein explained that a single mutation in a cell is unlikely to cause cancer, but if a person has more mutations, it is more likely that the cells will become cancerous.

Before now it was already well known that environmental factors, like smoking, as well as inherited genetic mutations were a leading cause of cancer. Whether a few malignant cells form a unsafe tumor depends on, among other things, levels of inflammation, insulin, and obesity.

Investigators at Johns Hopkins University in Baltimore used complex mathematical modeling to track mutations driving abnormal cell growth for 32 types of cancer. “They are assuming that just because tissues which have high stem cell turnover also have high cancer rates, that one is causing the other”, says cancer researcher Anne McTiernan of the Fred Hutchinson Cancer Research Center in Seattle.