Breast Cancer Risk Elevated if Epigenetic Clock Runs Fast

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The risk of cancer correlates with age, which may be measured in various ways. The easiest measure—chronologic age—may not be the best. Instead, cancer risk may be better estimated by measuring biologic age, which is a matter of how well the body is working—or how well the body can be expected to work, given the state of the body’s DNA.

During normal aging, DNA accumulates methyl groups, epigenetic marks, at a rate that is faster or slower in different people. If the epigenetic clock runs fast, biologic age may exceed chronologic age, with implications for cancer risk.

How much might the risk of breast cancer be elevated when the epigenetic clock runs fast? To answer that question, scientists based at The National Institute of Environmental Health Sciences (NIEHS) measured baseline blood DNA methylation and looked for an association with the risk of developing breast cancer. The scientists, led by Jack A. Taylor, MD, PhD, senior investigator, NIEHS, determined that such an association does in fact exist.

“We found that if your biologic age is older than your chronologic age, your breast cancer risk is increased,” said Taylor. “The converse was also true. If your biologic age is younger than your chronologic age, you may have decreased risk of developing breast cancer.”

Details of the study appeared February 22 in the Journal of the National Cancer Institute, in an article entitled, “Methylation-based biological age and breast cancer risk.” The article indicates that the NIEHS team examined data from the Sister Study, a group of more than 50,000 women in the United States and Puerto Rico. In the Sister Study, methylation data was available for a subset of 2764 women, all of whom were cancer-free at the time of blood collection.

The study also specifies that the NIEHS team assessed the degree of methylation at three different DNA regions. Essentially, the team consulted three different epigenetic clocks.

Each of the three clocks showed that biological age acceleration was statistically significantly associated with increased risk of developing breast cancer,” the article’s authors wrote. “For one of the clocks, each five-year acceleration in biological age corresponded with a 15% increase in breast cancer risk.”

The authors also noted that although biological age may accelerate with menopausal transition, age acceleration in premenopausal women independently predicted breast cancer.

The scientists speculated that biologic age could be related to environmental exposure. “However, we don’t yet know how exposures and lifestyle factors may affect biologic age,” Taylor admitted, “or whether this process can be reversed.”

Lead author Jacob Kresovich, PhD, a fellow in the Taylor group, had read studies that used epigenetic clocks to predict age-related mortality. Since age is the leading risk factor for breast cancer, he hypothesized that age acceleration may be associated with higher breast cancer risk.

“If you look at a group of people who are all the same age, some may be perfectly healthy while others are not,” Kresovich said. “That variability in health may be better captured by biologic age than chronologic age.”

Kresovich suggests that using DNA methylation to measure biologic age may help scientists better understand who is at risk for developing cancer and other age-related diseases. This research is an example of epigenetics, a field that studies how biochemical processes turn individual genes on or off, without affecting the DNA sequence.

The Taylor group plans to continue using epigenetic data, along with information on genetics, environment, and lifestyle to better understand how these factors interact and contribute to disease risks.

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