Biological age, which is a DNA-based estimate of a person’s age, is linked to future development of breast cancer, according to NIEHS scientists in a study published online February 22 in the Journal of the National Cancer Institute.
They determined biological age by measuring DNA methylation, which is a chemical change to DNA that is part of the normal aging process. The study showed that for every five years a woman’s biological age was older than her chronological or actual age, known as age acceleration, she had a 15 percent increase in her chance of developing breast cancer.
The researchers speculated that biological age might be tied to environmental exposures. If so, it might be a useful indicator of disease risk. They used three different measures, called epigenetic clocks, to develop biological age estimates. These clocks measured methylation at specific locations in DNA. Scientists used these clocks to estimate biological age, which could then be compared with chronological age.
Sister Study data
The team 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 U.S. and Puerto Rico. The study was 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 their blood samples were drawn.
"We found that if your biological age is older than your chronological age, your breast cancer risk is increased,” said corresponding author Jack Taylor, M.D., Ph.D., head of the NIEHS Molecular and Genetic Epidemiology Group. “The opposite was also true. If your biological age is younger than your chronological age, you may have decreased risk of developing breast cancer. However, we do not yet know how exposures and lifestyle factors may affect biological age or whether this process can be reversed."
Lead author Jacob Kresovich, Ph.D., a postdoctoral fellow in the Taylor group, had read studies that used epigenetic clocks to predict age-related mortality. Because age is the leading risk factor for breast cancer, he thought that age acceleration might 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 biological age than chronological age."
Kresovich suggested that using DNA methylation to measure biological age might 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 researchers plan 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.
Epigenetic aging in response to environmental exposures is key to the effects of bisphenol A (BPA) exposure, as discussed in the February NIEHS Distinguished Lecture, by Cheryl Walker, Ph.D., from Baylor College of Medicine. See the story in this issue.
Citation: Kresovich JK, Xu Z, O’Brien KM, Weinberg CR, Sandler DP, Taylor JA.. 2019. Methylation-based biological age and breast cancer risk. J Natl Cancer Inst; doi:10.1093/jnci/djz020 [Online 22 February 201].