• Posted February 3, 2025

Lifetime Cancer Risk Might Be Set Before You're Born

A person’s lifetime risk of cancer might be partly established before they are even born, a new mouse study says.

Researchers identified two distinct genetic states that arise during fetal development and are linked to cancer risk, according to a report published recently in Nature Cancer.

One of these states is associated with a higher lifetime risk of cancer, and the other with a lower risk, researchers noted.

“Our identification of these two epigenetically different states open the door to an entirely new world of study into the underpinnings of cancer,” senior researcher J. Andrew Pospisilik, chair of epigenetics at the Van Andel Institute in Grand Rapids, Mich., said in a news release.

Findings also show that if cancer develops in the high-risk state, it’s more likely to be a solid tumor such as lung or prostate cancer. The low-risk state makes liquid tumors like leukemia or lymphoma more likely.

Cancer risk increases as people age, due to accumulating DNA damage and other factors, researchers said in background notes.

However, not every abnormal cell goes on to become cancer, leading doctors to explore other influences like genetics as potential additional contributors to cancer.

“Everyone has some level of risk but, when cancer does arise, we tend to think of it just as bad luck,” lead researcher Ilaria Panzeri, a research scientist in Pospisilik’s lab, said in a news release.

“However, bad luck doesn’t fully explain why some people develop cancer and others don’t,” she said. “Most importantly, bad luck cannot be targeted for treatment.”

For the study, researchers focused on the gene TRIM28. That gene plays an important role in silencing or regulating other genes, including genes linked to cancer.

The team found that mice with reduced levels of TRIM28 could fall into one of two patterns when it comes to the expression of their cancer-related genes, despite being otherwise identical.

Those patterns are established during their fetal development, and the strength of the patterns determines which of the two cancer risk states will be in place throughout their lifetime.

These same genetics are frequently mutated in human cancer, researchers noted.

“Our findings show that cancer’s roots may start during the sensitive period of development, offering a new perspective to study the disease and potential new options for diagnosis and treatment,” Panzeri said.

Researchers also found evidence of the two different states in tissues throughout the bodies of the mice, suggesting that this developmental risk might be common across cancers.

In the future, the researchers plan to explore the effects of these two states when it comes to individual types of cancer.

More information

The National Cancer Institute has more on the genetics of cancer.

SOURCE: Van Andel Institute, news release, Jan. 27, 2024