A new groundbreaking study by scientists at the Van Andel Institute suggests that the risk of cancer in a person’s lifetime may begin even before birth.
The research, published in Nature Cancer, discovered two different epigenetic states that develop during the course of growth and are associated with varying levels of cancer risk. One state corresponds to a lower lifetime cancer risk, while the other is linked to a higher risk.
If cancer emerges in the low-risk state, it is more likely to manifest as a liquid tumor, such as leukemia or lymphoma. In contrast, cancers that arise from the high-risk state are more often solid tumors, like lung or prostate cancer.
“Traditionally, cancer has been seen mainly as a genetic or mutation-driven disease that manifests later in life, but our findings shift this understanding,” explained Dr. J. Andrew Pospisilik, the chair of VAI’s Department of Epigenetics and a co-corresponding author of the study. “By pinpointing these two distinct epigenetic states, we’ve opened up a fresh avenue for investigating the foundational aspects of cancer.”
As people age, their cancer risk tends to increase due to the build-up of DNA damage among other influences. However, not all abnormal cells develop into cancer. In recent studies, scientists have also recognized the role of epigenetic errors as additional factors contributing to cancer development.
Epigenetics refers to mechanisms that determine how and when DNA instructions are executed. Disruptions in epigenetic processes can compromise cellular quality control, allowing unhealthy cells to survive and proliferate.
In their research, Pospisilik and his team found that mice with lower levels of the gene Trim28 displayed one of two patterns of epigenetic modifications on genes linked to cancer, despite having otherwise similar conditions. These patterns form during development, and their strength dictates which cancer risk state is present.
“While everyone has some inherent level of risk, we often attribute the development of cancer to mere bad luck,” stated Dr. Ilaria Panzeri, a research scientist in the Pospisilik Lab and a co-author of the study. “Yet, bad luck alone does not clarify why certain individuals get cancer while others do not. More importantly, bad luck is not something that can be targeted for treatment. On the other hand, epigenetics can be addressed directly. Our research indicates that the origins of cancer might begin during crucial developmental periods, providing a novel perspective for researching the disease and uncovering potential new diagnostic and treatment options.”
The research team identified the presence of these two epigenetic states across various tissues, indicating that developmental epigenetic risk may be prevalent across different types of cancer. Moving forward, they intend to investigate how these distinct states impact specific cancer forms.
Additional authors include Luca Fagnocchi, Ph.D., Stefanos Apostle, M.S., Megan Tompkins, Emily Wolfrum, MPH, Zachary Madaj, M.S., Galen Hostetter, M.D., Yanqing Liu, Kristen Schaefer, Chih-Hsiang Yang, Ph.D., Alexis Bergsma, Ph.D., Anne Drougard, Ph.D., Erez Dror, Ph.D., Darrell Chandler, Ph.D., and Timothy J. Triche, Jr., Ph.D., from VAI; the PERMUTE Consortium; and Daniel Schramek, Ph.D., from the University of Toronto. Schaefer also has ties with Case Western Reserve University.
