Cancer risk from one gene appeared mainly acquired in midlife

Inherited variants clustered at sites linked to partial loss of the gene’s protein function and a lower likelihood of developing disease. Variants classically linked to Li-Fraumeni syndrome, an inherited cancer-predisposition disorder, appeared predominantly acquired. When abundant in blood, these variants were associated with markedly greater risk of blood cancers, but not solid tumors. The findings pointed to an important contribution from expanding groups of blood cells carrying acquired variants. The authors concluded that acquired rather than inherited risk predominated in healthy middle-aged adults.