Breast cancer’s spread may be influenced by gene affecting circadian rhythms

Variations in a gene involved in so-called circadian rhythms that control everything from cell division to sleep may also promote the spread of breast cancer to other organs, a new study suggests.

In mouse studies, researchers showed how having slightly different versions of gene called Arntl2 can aid the spread of cancer cells. When they analyzed the genes of breast cancer patients, they also found that at least one version of Arntl2 was indeed linked to how long the women survived disease-free.

“Our results suggest that there is a link between inherited factors that may influence how well circadian rhythms may be regulated and the probability that breast cancer will spread,” said senior study author Kent Hunter, a researcher at the National Cancer Institute in Bethesda, Maryland.

The activity of Arntl2, which regulates when and if certain other genes are activated, can affect whether a common, hard-to-treat type of malignancy known as estrogen receptor negative breast cancer will spread, becoming more lethal, Hunter and his colleagues write in the journal PLOS Genetics.

When breast cancer doesn’t spread, 99 percent of women survive at least five years after their diagnosis, the authors note. But when it does spread, or metastasize, five-year survival odds plummet to 26 percent.

With estrogen receptor negative tumors, hormone therapy is unlikely to work, leaving women with fewer treatment options than they might have with other types of breast cancer.

The study found that one particular version of Arntl2 was associated with a 29 percent lower risk of death for women who had it. That could guide treatment of women with this or other inherited versions of the gene, and it also makes the gene a potential target for new drug development, the researchers note.

This and other “clock genes” have previously been linked to cancer risk, and so have sleep patterns, which are also regulated by circadian rhythms in the body.

“We know that regular sleep is an important part of our circadian rhythm, and we know that much of our health, particularly with regard to DNA repair when we talk about cancer, is regulated by our circadian rhythm,” said Cheryl Thompson, a researcher at Case Western Reserve University who wasn’t involved in the study.

“There is still more work to be done to see if sleeping longer or getting better quality sleep can decrease your risk of getting cancer, or likelihood of getting an aggressive cancer,” Thompson added by email.

Women, of course, can’t control whether they will inherit a genetic variation in the Arntl2 gene, noted Amanda Phipps, an epidemiology researcher at the University of Washington who wasn’t involved in the study.

“However, beyond this study, there is increasing evidence to support the health benefits of good quality sleep,” Phipps said by email. “In our own research, we recently found that breast cancer survival was poorest among women who reported, before their breast cancer diagnosis, that they typically received less than 6 hours of sleep per night.”

In terms of cancer prevention, women are traditionally advised to focus on lifestyle factors such as eating well and getting enough exercise, and avoiding smoking or too much alcohol, Phipps added.

“However, with growing recognition as to the health implications of poor quality and insufficient sleep, it is plausible that cancer prevention efforts could expand to encompass recommendations for healthy sleep,” Phipps said.