Biologic Age and Elevated Risk of Breast Cancer

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Biologic age—a DNA-based estimate of a person’s age—may be associated with the development of breast cancer, according a report published by Jacob K. Kresovich, PhD, of the National Institute of Environmental Health Sciences (NIEHS), and colleagues in the Journal of the National Cancer Institute.1

Study Methods

Scientists from the NIEHS, part of the National Institutes of Health, speculated that biologic age may be tied to environmental exposures; if so, it may be a useful indicator of disease risk. Biologic age was determined by measuring DNA methylation, a chemical modification to DNA that is part of the normal aging process.

Jacob K. Kresovich, PhD

Jacob K. Kresovich, PhD

Researchers used three different measures, called epigenetic clocks, to estimate biologic age, which can then be compared with chronologic age. These clocks—Hannum, Horvath, and Levine—measure methylation found at specific locations in DNA.

The researchers used DNA from blood samples provided by women enrolled in the NIEHS-led Sister Study, a group of more than 50,000 women in the United States and Puerto Rico. The study was specifically designed to identify environmental and genetic risk factors for breast cancer. The research team measured methylation in a subset of 2,764 women, all of whom were cancer-free at the time of blood collection.

Key Findings

Each of the three clocks used showed that biologic age acceleration was statistically significantly associated with an increased risk of breast cancer (Hannum’s clock: hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.00–1.21, P = .04; Horvath’s clock: HR = 1.08, 95% CI = 1.00–1.17, P = .04; Levine’s clock: HR = 1.15, 95% CI: 1.07–1.23, P < .001). For Levine’s clock, every 5 years a woman’s biologic age was older than her chronologic or actual age—known as age acceleration—she had a 15% increase risk of developing breast cancer.

We found that if your biologic age is older than your chronologic age, your breast cancer risk is increased.
— Jack A. Taylor, MD, PhD

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“We found that if your biologic age is older than your chronologic age, your breast cancer risk is increased. The converse was also true. If your biologic age is younger than your chronologic age, you may have decreased risk of developing breast cancer,” said corresponding author Jack A. Taylor, MD, PhD, Head of the NIEHS Molecular and Genetic Epidemiology Group. “However, we don’t yet know how exposures and lifestyle factors may affect biologic age or whether this process can be reversed.”

Dr. Kresovich, a postdoctoral fellow in Dr. Taylor’s 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 a 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,” Dr. Kresovich said. “That variability in health may be better captured by biologic age than chronologic age.”

Dr. Kresovich also suggested 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.

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. 

DISCLOSURE: The study authors’ full disclosures can be found at


1. Kresovich JK, Xu Z, O’Brien KM, et al: Methylation-based biological age and breast cancer risk. J Natl Cancer Inst. February 22, 2019 (early release online).