Counting genetic mutations predicts how soon you’ll get cancer

How young will you be when you get cancer? The number of mutations you have in different genes can bring that date closer.

We already know that mutations in cancer genes like BRCA1 and BRCA2 increase cancer risk. But now David Thomas at the Garvan Institute of Medical Research in Sydney and his colleagues have shown for the first time that mutations in genes associated with a lower cancer risk can little by little add up to an even deadlier effect.

The team compared the genetic profiles of healthy individuals with those of 1162 people with sarcomas – cancers that develop in bones and soft tissue and disproportionately affect young people. In particular, they focused on 72 genes – some strongly linked to sarcoma, like the TP53 gene, and others that are only weakly linked.

As they expected, a mutation in the TP53 gene increased a person’s sarcoma risk – half developed cancer by the age of 32. But people with mutations in two genes only weakly associated with sarcoma developed tumours at a younger age – half had cancer by the age of 25. This effect was even stronger in those who had three or more mutations in such genes.

“Cancer is a disease where you accumulate stepwise genetic variants,” says Thomas. “This means that the more genetic variation you carry, the earlier in life you’re likely to develop it.”

Looking across multiple genes should allow cancers to be detected sooner, before they become fatal, says Thomas. It may one day become routine to screen people for high-risk combinations of mutations in genes previously considered to have little relevance to cancer risk.