Johnson KC, et al., 2017

Researchers in this study explored how aging might increase the risk of breast cancer by looking at DNA changes in healthy breast tissue. They focused on DNA methylation—a natural process that helps control which genes are turned on or off. Using samples from 100 cancer-free women who donated to the Komen Tissue Bank, the scientists analyzed how common breast cancer risk factors such as age, body weight, and family history might influence DNA methylation patterns. They found that age, more than any other factor, was linked to specific changes in the DNA of breast tissue. These changes were found at regions of the genome that help regulate how cells grow and divide, and many of them were also found in breast cancer tissue, suggesting a possible early step in cancer development.

Importantly, this study shows how valuable the Komen Tissue Bank is for understanding cancer risk before any disease is present. By analyzing healthy tissue from a diverse group of women, researchers were able to uncover how aging alone may "prime" cells for disease by altering the epigenetic landscape. These findings suggest that some of the first biological changes that lead to breast cancer may start long before any tumor forms. Understanding these early changes can help scientists find new ways to predict, prevent, or delay breast cancer in women as they age.

Full-Text Journal Article PubMed

What did they study?

This study investigated how established breast cancer risk factors—especially age—are linked to changes in DNA methylation within normal breast tissue. DNA methylation is a chemical modification that can influence whether certain genes are active or inactive. Using an epigenome-wide approach, the researchers looked for patterns of methylation at over 390,000 locations in the genome and examined how these patterns were related to factors such as age, body mass index (BMI), reproductive history, and family history of breast cancer. They also explored whether these age-related DNA changes were more likely to appear in early or invasive breast cancers, aiming to better understand the biological mechanisms that might connect aging to increased cancer risk.

What did they find?

• Age is the only risk factor strongly linked to DNA methylation changes in normal breast tissue, with 787 genomic sites showing significant age-related patterns, while other factors like BMI, childbirth history, and family history showed no strong associations.
• Most age-related changes involved increased methylation at key regulatory regions of the genome, particularly at enhancer elements and binding sites for chromatin remodelers like MYC and CTCF, which help control gene activity.
• These age-related changes were validated in other datasets and were more likely to be found in both pre-invasive and invasive breast cancer tissues, suggesting they may be early markers of disease development.
• Breast tissue shows signs of accelerated biological aging, especially in African American and Hispanic women, which may point to broader health disparities and reinforce the link between aging and increased breast cancer risk.

Why is this study important?

This study helps explain how aging, the strongest risk factor for breast cancer, may influence disease development at the molecular level. By identifying specific DNA changes that occur naturally with age in healthy breast tissue, researchers can better understand the earliest steps that may lead to cancer. These findings highlight the potential for using age-related DNA methylation patterns as early warning signs or targets for prevention. Additionally, the discovery of accelerated biological aging in certain racial groups points to possible health disparities and underscores the need for more inclusive research. Overall, this work brings scientists closer to finding ways to predict, prevent, or delay breast cancer before it begins.

Full citation

Johnson KC,Houseman EA,King JE,Christensen BC Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age.. Breast cancer research : BCR 2017 Jul; 19 (1). PMID:28693600.