CanRes: The rate at which mutations accumulate in cells may determine cancer risk

The rate at which mutations accumulate in cells may be one of the factors determining the risk of developing cancer: in some people, mutations accumulate significantly faster than in others. This was the conclusion reached by scientists from the Translational Genomics Research Institute (TGen) and City of Hope. The findings were published in the journal Cancer Research.

The researchers compared the DNA of healthy and cancerous tissues from seven organs: the bladder, colon, esophagus, liver, lungs, prostate, and stomach. They analyzed data from hundreds of normal tissue samples and thousands of tumor samples.

On average, cancer cells contained more than four times as many mutations as healthy cells. However, differences were also observed among people without cancer: even after accounting for age, some healthy participants had up to eight times more mutations in their tissues than others.

The authors suggest that this could help explain why cancer develops in some people at roughly the same age when others remain cancer-free. According to the so-called “tail hypothesis,” there is a small group of people in whom mutations accumulate more rapidly. The more such changes build up in cells over time, the greater the likelihood that mutations capable of triggering tumor development will arise.

The researchers compared this idea with two other explanations. According to the first, additional mutations emerge after cancer-associated changes have already occurred; according to the second, their accumulation is linked to rare, large-scale genomic damage. However, the “tail hypothesis” was most consistent with the data.

Scientists do not yet know why mutations accumulate faster in some people. They believe that assessing the rate of mutation accumulation in the future could help identify people at increased risk of cancer before a tumor develops and enable the development of more personalized prevention strategies.