Cancer risk has long been associated with aging, genetics, and lifestyle. Yet, a new study in Nature Cancer indicates that cancer risk could be found even before birth. Scientists at the Van Andel Institute (VAI) have discovered two unique epigenetic states during early development that might define a person's lifetime cancer risk.

Scientists have long assumed that cancer is largely the result of genetic mutations that build up over a lifetime. But this new study contradicts conventional knowledge by proposing that the cancer risk may be determined early in life. 

“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,” said J. Andrew Pospisilik, Ph.D., chair of VAI’s Department of Epigenetics and co-corresponding author of the study.

The research identified two epigenetic states—one with an increased risk of cancer and the other with decreased risk. Individuals carrying the lower-risk state might be more likely to get liquid tumors like leukemia or lymphoma, while those carrying the higher-risk state might be at greater risk for solid tumors, such as lung or prostate cancer.

What is Epigenetics

Epigenetics, or the change in gene expression without changing DNA sequences, is important to how cells work. Malfunctions in these processes can cause malfunctions in cellular quality control to permit defective cells to live and propagate. 

“Our identification of these two epigenetically different states opens the door to an entirely new world of study into the underpinnings of cancer,” Pospisilik noted.

Cancer risk is usually linked to age as a consequence of accumulated DNA damage and external factors. Nonetheless, scientists have stressed that not all abnormal cells become cancerous and hinted that underlying epigenetic factors may be in play.

To dig deeper, scientists investigated genetically identical mice with low amounts of the Trim28 gene. Both groups of mice had two different patterns of epigenetic marks on cancer-related genes. This finding suggests that developmental epigenetic risk could be widespread in many forms of cancer, providing important clues about where it comes from.

Could this lead to better cancer prevention?

The findings from the study present new opportunities for early detection and targeted prevention.

“Everyone has some level of risk but, when cancer does arise, we tend to think of it just as bad luck,” said Ilaria Panzeri, Ph.D., a research scientist in the Pospisilik Lab and the study’s first and co-corresponding author. “However, bad luck doesn’t fully explain why some people develop cancer and others don’t. Most importantly, bad luck cannot be targeted for treatment. Epigenetics, on the other hand, can be targeted.”

By learning about developmental epigenetic states that influence cancer risk, scientists hope to open the door to new prevention and treatment approaches. If these early signs can be detected and changed, it might be possible to prevent cancer before it arises.

This research is a major leap in cancer research, offering a new view of how and when cancer seeds are planted. 

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