Could Cancer Risk Be Set Before Birth?
For years, cancer has been seen as a disease of accumulated DNA damage, often linked to aging and environmental factors. But new research suggests that a person’s lifetime risk of cancer may begin before birth, influenced by genetic programming during fetal development.
The study, published in Nature Cancer, reveals that two distinct genetic states emerge early in development—one associated with a higher lifelong cancer risk and another linked to a lower risk. These findings challenge the traditional understanding of cancer’s origins and open the door to new approaches in early detection and treatment.
The Genetic States That Influence Cancer Risk
The research, led by J. Andrew Pospisilik, chair of epigenetics at the Van Andel Institute, examined how certain genetic mechanisms regulate cancer risk from the earliest stages of life.
Using mouse models, scientists identified two epigenetically distinct patterns:
- The high-risk state increases the likelihood of developing solid tumors like lung or prostate cancer.
- The low-risk state is more likely to result in blood cancers such as leukemia or lymphoma if cancer develops.
“Our identification of these two epigenetically different states opens the door to an entirely new world of study into the underpinnings of cancer,” Pospisilik said in a statement.
Bad Luck or Predetermined Risk?
Cancer has often been attributed to random genetic mutations, lifestyle factors, and sheer bad luck. But this study suggests that some of that risk may be predetermined before birth, even before external influences come into play.
“Everyone has some level of risk, but when cancer does arise, we tend to think of it just as bad luck,” said lead researcher Ilaria Panzeri, a scientist in Pospisilik’s lab.
“However, bad luck doesn’t fully explain why some people develop cancer and others don’t,” she added. “Most importantly, bad luck cannot be targeted for treatment.”
The Role of the TRIM28 Gene
At the center of this discovery is a gene called TRIM28, which plays a crucial role in silencing or regulating other genes, including those linked to cancer.
The researchers found that mice with reduced TRIM28 levels followed one of two genetic expression patterns, despite being genetically identical. These patterns were established during fetal development and persisted throughout their lifetime, influencing whether they carried a higher or lower risk of developing cancer.
Importantly, TRIM28 mutations are frequently found in human cancers, suggesting that these genetic states may also exist in people.
A New Way to Think About Cancer Prevention
The study’s findings have wide-reaching implications. If cancer risk can be shaped before birth, researchers may one day develop new diagnostic tools to identify high-risk individuals early on.
“Our findings show that cancer’s roots may start during the sensitive period of development,” Panzeri explained. “This offers a new perspective for studying the disease and could lead to new options for diagnosis and treatment.”
What’s Next?
The research team plans to investigate how these genetic states influence different types of cancer in humans. Additionally, they hope to explore whether environmental or medical interventions could shift a person’s genetic state toward a lower-risk profile.
While it’s still early in the research, these discoveries suggest that the foundation for cancer risk might be built long before symptoms ever appear, reshaping how we think about cancer prevention, early detection, and personalized medicine.