New Insights Into How Genetic Differences Among Individuals Influence Breast Cancer Risk from Low-Dose Radiation

Scientists from the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) have identified tissue mechanisms that may influence a woman’s susceptibility or resistance to breast cancer after exposure to low-dose ionizing radiation, such as the levels used in full-body CT scans and radiotherapy.

The research could lead to new ways to identify women who have higher or lower risks of breast cancer from low-dose radiation. Such a predictive tool could help guide the treatment of cancer patients who may be better served by non-radiation therapies.

The findings also support the idea that a person’s genes play a big role in determining her risk of breast cancer from low-dose radiation. The current model for predicting cancer risk from ionizing radiation holds that risk is directly proportional to dose. But there’s a growing understanding that this linear relationship doesn’t apply at lower doses. Instead, the health effects of low-dose radiation may vary substantially among people depending on their genetic makeup.

The scientists, led by Andy Wyrobek of Berkeley Lab’s Life Sciences Division, report their research October 15 in the journal PLOS ONE.

They studied mammary tissue from two strains of mice—one that is susceptible to radiation-induced mammary gland cancer and one that is resistant—before and after the mice were exposed to low-dose radiation.

The team then looked for differences between the two strains in how their genes turn on and off. They used a method that scans thousands of genes simultaneously. They found differences in genes that regulate tissue stress response, DNA repair, immune response, cellular proliferation, and other cellular and tissue mechanisms.

They also found that these differences carried over to breast cancer survivability in women. Breast cancer patients with gene expression profiles like the cancer-resistant mice (before radiation exposure) were more likely to survive eight years after diagnosis. Women with gene expression profiles like the cancer-sensitive mice were less likely to survive after eight years.

Based on this, the scientists believe the cellular and tissue mechanisms that control mice’s risk of mammary gland cancer from low-dose radiation are similar to the mechanisms that affect a woman’s chance of surviving breast cancer.

“Our studies of genetic differences in radiation sensitivity in mice, and individual variation in breast cancer survival in women, suggest that there are women who, because of their genes, have a higher risk of breast cancer when they’re exposed to low-dose radiation,” says Andy Wyrobek, who conducted the research with Antoine Snijders, Joe Gray, and several other Berkeley Lab scientists.

“This raises the possibility that we can use gene expression profiles to develop simple tests that screen for women who may be sensitive to low-dose radiation versus women who are resistant,” Snijders says.