(© Feng Yu
– stock.adobe.com)
Scientists discover hidden patterns that could predict disease decades in advance
In a nutshell
- Early development matters: Scientists have discovered that patterns set before birth may influence your lifetime cancer risk, independent of genetic makeup. These patterns create two distinct groups with different susceptibilities to cancer.
- Different risks, different cancers: The research shows that these early-life patterns not only affect cancer risk levels but also influence the type of cancer that might develop — with one group more prone to blood cancers and the other to solid tumors.
- Prevention possibilities: Understanding these early developmental patterns could lead to new ways of identifying cancer risk early in life and developing preventive strategies, potentially stopping cancer before it starts.
GRAND RAPIDS, Mich. — When we bake two loaves of bread using the same recipe, subtle differences in temperature or mixing could lead to slightly different results. Even with identical ingredients and instructions, the outcome isn’t always identical. Scientists have just discovered that something similar happens in human development, and it might explain why some people are more likely to get cancer than others.
An intriguing new study from the Van Andel Institute suggests that tiny differences in our earliest stages of development — even before birth — might set the stage for cancer risk later in life. This discovery challenges what we thought we knew about cancer, which has traditionally been viewed mainly as a disease caused by genetic mutations that accumulate as we age.
“Most people think of cancer as bad luck,” explains Dr. Ilaria Panzeri, who led the research. “But bad luck doesn’t fully explain why some people develop cancer and others don’t. Most importantly, bad luck cannot be targeted for treatment.”
At the heart of this discovery is something called epigenetics, akin to a set of switches that can turn genes on or off without changing the genes themselves. These switches help control which instructions in our DNA get carried out and which remain dormant. When these switches don’t work properly, it can lead to health problems, including cancer.
The research team focused on a particular switch-operator called TRIM28. Using mice with reduced levels of TRIM28, they discovered something fascinating: identical mice naturally developed into two distinct groups with different cancer risks, despite having the exact same genes. One group tended to be lighter in weight, while the other was heavier; but the real differences went far deeper than appearance.
Even more interesting was how these differences affected the types of cancer that developed. Mice in one group were more likely to develop blood cancers like leukemia, while the other group showed higher rates of solid tumors, like lung or prostate cancer. These differences could be detected in tissue samples taken when the mice were just 10 days old – long before any visible signs of disease appeared.
“Because most cancers occur later in life and are understood as diseases of mutation, or genetics, there hasn’t been a deep focus on how development might shape cancer risk. Our findings change that,” explains Dr. Andrew Pospisilik, who helped lead the research. He notes that while we can’t change our genes, we might be able to influence these genetic switches, potentially leading to new ways to prevent or treat cancer.
When the scientists looked at human cancer databases, they found patterns comparable to their findings. Patients with changes in the human versions of the genes affected in the mice tended to have worse cancer outcomes, suggesting these early-life patterns might be important in human cancer too.
What makes the study, which is published in Nature Cancer, particularly exciting is its potential for cancer prevention. If doctors could identify these risk patterns early in life, they might be able to develop strategies to prevent cancer before it starts. It’s like having an early warning system that could help identify who might benefit most from enhanced screening or preventive measures.
Much work remains to be done, but this study marks a crucial step toward understanding — and potentially preventing — cancer at its earliest origins.
Paper Summary
Methodology
The scientists studied mice with a modified version of the TRIM28 gene over 70 weeks – roughly equivalent to following humans from childhood through middle age. They regularly measured body composition and tracked tumor development. By analyzing tissue samples taken at different times, including when the mice were just 10 days old, they could see how early-life patterns related to later cancer risk.
Results
The study revealed that mice with reduced TRIM28 naturally developed into two groups with different cancer risks. The lighter mice developed cancer more quickly and were more likely to get multiple types of cancer. By analyzing DNA from very young mice, the researchers could predict which group they would belong to, suggesting these patterns are set very early in life.
Limitations
While this research is exciting, it’s important to note that it was mainly done in male mice, as females showed lower cancer rates that made it harder to study the patterns. Also, while the findings suggest these early-life patterns are important for cancer risk, more research is needed to understand exactly how they work in humans.
Discussion and Takeaways
This discovery could change how we think about cancer prevention. Instead of focusing only on lifestyle factors like diet and exercise, or genetic risk factors we inherit from our parents, scientists might now look at ways to influence these early-life patterns that affect cancer risk. While this research is still in its early stages, it opens up exciting new possibilities for understanding and potentially preventing cancer.
Funding and Disclosures
This study was made possible through support from several organizations, including the Max Planck Society, the European Research Council, Van Andel Institute, the National Institutes of Health, and the Chan Zuckerberg Initiative. The researchers reported no conflicts of interest.
Publication Details
The study, titled “TRIM28-dependent developmental heterogeneity determines cancer susceptibility through distinct epigenetic states,” was published in Nature Cancer on January 24, 2025.
