DNA modifications in breast cancer risk genes may be a result of combined genetic and environmental causes, BCRF investigators report
Key Takeaways
- Genetics and environment both influence breast cancer risk.
- BCRF researcher Dr. Mary Beth Terry shares an update on the LEGACY Girls study, which is investigating risk in healthy girls.
- Ongoing work in epigenetics, early-life exposures, and personalized risk assessment is helping researchers develop more personalized prevention strategies.
A complex mix of factors influences breast cancer risk, raising an important question: Is the risk primarily genetic or environmental? While some cases are linked to inherited gene mutations, others may be shaped by environmental exposures and biological changes over time.
Understanding how these influences work together is critical for improving prevention, identifying risk earlier, and developing more personalized approaches to care.
Researchers are now exploring how genetics and environment interact at a deeper level, including how these factors may affect the body long before cancer develops.
Is breast cancer genetic or environmental?
There are both genetic and environmental risk factors for breast cancer. While inherited gene mutations can increase risk, environmental exposures and biological processes can also affect how and when the disease develops. Rather than a single cause, breast cancer risk is shaped by how these factors interact over time—an area researchers are continuing to study.
The key to understanding the causes of breast cancer is identifying DNA-damaging events that result from exposure to harmful chemicals in the environment long before breast cancer is detected.
With BCRF support, Drs. Mary Beth Terry and Regina Santella of Columbia University in New York launched The LEGACY Girls Study in 2011, a study that consisted of 1,040 healthy young girls. One of several long-term breast cancer research studies, it was designed to understand the influence of genetics, behavior, environment, and diet on puberty in girls aged 6 to 13 years.
“If it were not for BCRF funding of the LEGACY pilot studies, we would not have been able to assemble this cohort,” Dr. Terry said. “It is very difficult to get funding to study normal mammary gland development, but our BCRF-supported work made it possible to get funding from the National Institutes of Health to continue the project along with BCRF’s sustained support.”
Genetic risk factors for breast cancer
Findings from breast cancer studies are helping researchers better understand how risk develops at a biological level. The best-known genetic risk factors are mutations in BRCA1 and BRCA2 genes, but research has revealed several others. In a 2018 article published in the journal Epigenetics, Drs. Terry and Santella—along with colleagues Dr. Hui Chen Wu of Columbia University and Drs. Benjamin Tycko and Catherine Do of Hackensack University Medical Center—reported new findings from the study.
The team found that DNA modifications in two genes implicated in breast cancer risk were detected in the white blood cells of young girls with a family history of breast cancer. These DNA modifications were not found in girls who did not have a family history of the disease.
The alterations were identified in the ESR1 and SEC16B genes. ESR1 codes for the estrogen receptor (a known driver in more than 70 percent of breast cancers). The SEC16B gene regulates the age a girl begins menstruation and is involved in obesity—two factors implicated in breast cancer risk.
What is DNA methylation, and why does it matter?
Both genes had modified DNA where an enzyme attached a chemical compound (a methyl group) onto the DNA. This is called DNA methylation and it can alter the gene’s expression. However, DNA methylation is not an inherited genetic alteration and can be reversed. Instead, it’s an epigenetic alteration, one that is caused by a modification to the DNA, not an alteration in the genetic code itself. Epigenetics is the study of how cells turn different genes “on” and “off” without changing DNA sequence.
A person could be born with a genetic alteration, such as a single nucleotide polymorphism (or SNP), in a gene that regulates methylation. Inheriting such a SNP could increase the amount of DNA methylation in a particular gene. In fact, that is what the researchers found. “This is the first study to show that girls with a breast cancer family history have epigenetic differences compared with girls without a breast cancer family history,” Dr. Terry noted. “Our findings support that in addition to genetic differences, girls with a breast cancer family history may have different susceptibility to breast cancer based on epigenetic differences.”
Environmental risk factors for breast cancer
Environmental risk factors for breast cancer include exposure to certain chemicals, pollutants, and lifestyle-related influences that can affect how genes function over time.
Many environmental factors can influence DNA methylation, which is widely recognized as a factor in cancer development. Polycyclic aromatic hydrocarbons (PAH) and bisphenol A (BPA) are two prevalent environmental pollutants. Both have been shown to cause DNA methylation in laboratory models and humans. Maternal smoking has also been shown to increase DNA methylation in offspring.
Drs. Terry and Santella plan to continue to follow the LEGACY girls to see what kinds of environmental exposures affect these epigenetic changes and if they are driven by genetic differences. Read more about their BCRF research on the Meet the Researchers page.
The Bottom Line
Research into how genetic and environmental factors influence breast cancer risk continues to evolve, with scientists building on studies like the LEGACY Girls Study to better understand how risk develops over time. Ongoing work in areas such as epigenetics, early-life exposures, and personalized risk assessment is helping researchers move closer to more precise prevention strategies.
Progress like this depends on sustained investment in research. Breakthroughs that deepen our understanding of breast cancer risk—and how to reduce it—are made possible through funding that supports long-term studies and scientific innovation.
Help fund the research driving these discoveries and support the next generation of breakthroughs in breast cancer prevention.
Frequently asked questions about breast cancer risk research
What are the main risk factors for breast cancer?
A combination of genetic, environmental, and lifestyle factors influence breast cancer risk. Inherited gene mutations, such as those in BRCA genes, can increase risk, while environmental exposures, hormonal factors, and lifestyle choices (like smoking or excessive drinking) [EG1] may also play a role. Researchers are continuing to study how these factors interact over time.
Can environmental factors increase breast cancer risk?
Yes, environmental factors can contribute to breast cancer risk by affecting how genes function. Exposure to certain chemicals and pollutants, as well as lifestyle-related influences like smoking and obesity, may lead to biological changes such as DNA methylation. This may impact how cells grow and behave.
Is breast cancer hereditary?
Some breast cancers are hereditary, meaning they are linked to inherited genetic mutations passed down through families. However, most breast cancer cases are not caused by inherited genes alone and instead result from a combination of factors such as genetic predisposition, environmental influences, and more.
How are researchers studying breast cancer risk today?
Researchers are examining how genetics, environmental exposures, and biological processes interact. Long-term studies, like those supported by BCRF, are helping scientists understand how risk develops over time and how it may be reduced through prevention strategies.
