Like snowflakes, all of us are a little different, even genetically identical twins or clones. But why do individuals with matching DNA vary? And how do those nongenetic differences affect risk of genetically influenced diseases like cancer?

Whether a mutation manifests, and how strongly, comes down to cellular physiology. New work from scientists at Fred Hutchinson Cancer Research Center and the University of Washington shows that a cell’s capacity to turn genes into proteins influences its characteristics, or phenotype. Using genetically identical worms, they observed that differences in this capacity influence how strongly a cancer-related mutation changes a worm’s characteristics. Published in the journal Nature Communications, the study also showed that protein-expression capacity also underlies differences in worm lifespans.

The findings establish that “general cell-to-cell differences in the ability to make genes into proteins have phenotypic consequences,” said Fred Hutch’s Dr. Roger Brent, who co-led the study.

Though the team studied genetically identical worms, he suspects that differences seen in genetically variable populations, such as humans, could also be attributed to this phenomenon. The findings could help explain why only certain mutated cells turn cancerous, or why only certain members of a family carrying the same disease-causing mutation get that disease.

If this basic insight into cellular physiology extends from worms to people, it could have ramifications for treating disease, Brent said. Many promising cancer drugs differ greatly in their effectiveness in individual cancer patients. Finding ways to reduce natural variation in cell behavior could help improve drug efficacy by making all of a patient’s cancer cells respond to a drug in the same way, or by improving the chances that a drug will be similarly effective in every patient.

Like snowflakes, all of us are a little different, even genetically identical twins or clones. But why do individuals with matching DNA vary? And how do those nongenetic differences affect risk of genetically influenced diseases like cancer?

Whether a mutation manifests, and how strongly, comes down to cellular physiology. New work from scientists at Fred Hutchinson Cancer Research Center and the University of Washington shows that a cell’s capacity to turn genes into proteins influences its characteristics, or phenotype. Using genetically identical worms, they observed that differences in this capacity influence how strongly a cancer-related mutation changes a worm’s characteristics. Published in the journal Nature Communications, the study also showed that protein-expression capacity also underlies differences in worm lifespans.

The findings establish that “general cell-to-cell differences in the ability to make genes into proteins have phenotypic consequences,” said Fred Hutch’s Dr. Roger Brent, who co-led the study.

Though the team studied genetically identical worms, he suspects that differences seen in genetically variable populations, such as humans, could also be attributed to this phenomenon. The findings could help explain why only certain mutated cells turn cancerous, or why only certain members of a family carrying the same disease-causing mutation get that disease.

If this basic insight into cellular physiology extends from worms to people, it could have ramifications for treating disease, Brent said. Many promising cancer drugs differ greatly in their effectiveness in individual cancer patients. Finding ways to reduce natural variation in cell behavior could help improve drug efficacy by making all of a patient’s cancer cells respond to a drug in the same way, or by improving the chances that a drug will be similarly effective in every patient.