Our lifetime cancer risk may be established before we are born

What if your risk of developing cancer was already determined before your birth? While scientists have long believed cancer results primarily from genetic mutations and environmental exposures, a recent study suggests a different possibility.

Researchers at Van Andel Institute have discovered that cancer susceptibility may be programmed in the womb, influenced by epigenetic states formed during early development.

Early development and cancer risk

“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,” noted J. Andrew Pospisilik, Ph.D., chair of Van Andel Institute’s Department of Epigenetics.

“Our findings change that. Our identification of these two epigenetically different states open the door to an entirely new world of study into the underpinnings of cancer,”

A study published in the journal Nature Cancer has identified two distinct epigenetic states that emerge during development.

One of these states corresponds with a lower lifetime cancer risk, while the other is associated with a significantly higher risk.

These findings suggest that cancer risk isn’t just a matter of bad luck or lifestyle choices but may be set in motion before birth.

Epigenetics in cancer risk

Epigenetics governs how and when genes are expressed, influencing cell function without altering DNA sequences.

Unlike genetic mutations, which permanently change DNA, epigenetic modifications are reversible and influenced by environmental factors.

Errors in these processes can weaken the body’s ability to regulate cell growth and division, potentially increasing cancer susceptibility.

The study highlights how developmental epigenetic differences contribute to cancer risk. If cancer arises in the lower-risk state, it tends to manifest as a liquid tumor, such as leukemia or lymphoma.

Conversely, individuals in the higher-risk state are more prone to solid tumors, including lung and prostate cancer.

These findings suggest that cancer susceptibility is shaped by biological processes that occur before birth, rather than being entirely the result of mutations acquired over time.

Distinct genetic patterns

The researchers focused on the gene Trim28, which plays a key role in maintaining epigenetic stability. They found that mice with reduced levels of Trim28 exhibited one of two distinct epigenetic patterns on cancer-related genes.

These patterns, established during development, influence an individual’s likelihood of developing cancer later in life.

“Everyone has some level of risk but, when cancer does arise, we tend to think of it just as bad luck,” said Dr. Ilaria Panzeri, a research scientist in the Pospisilik Lab and the study’s first 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. 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.”

These results challenge conventional perspectives on cancer development. Traditionally, cancer is considered a disease of accumulated mutations and DNA damage.

However, this study indicates that epigenetic mechanisms set in motion before birth may influence cancer risk decades later. The findings open new avenues for research into cancer prevention and early diagnosis.

Lifelong impact of epigenetic states

The study found evidence of these two epigenetic states across various tissues in the body. This suggests that developmental epigenetic risk may not be limited to one type of cancer but could apply to multiple forms of the disease.

The presence of these epigenetic markers across different organs implies a systemic impact, possibly affecting cancer risk throughout the entire body.

Cancer risk increases as individuals age, primarily due to the accumulation of DNA damage and exposure to environmental factors.

However, not every abnormal cell progresses into cancer. This study highlights how epigenetic processes established early in life may influence whether or not precancerous cells become malignant. Understanding these early changes provides a valuable opportunity for intervention.

New directions for cancer research

The research team plans to investigate how these two epigenetic states affect specific types of cancer in future studies.

By identifying the molecular pathways that distinguish high-risk and low-risk epigenetic states, scientists could develop strategies to shift individuals toward the lower-risk state.

This could lead to potential new treatments aimed at modifying epigenetic patterns before cancer develops.

Future research will explore whether external factors, such as diet, stress, or environmental toxins, influence these epigenetic states.

Cancer prevention strategies

If researchers can identify ways to alter these genetic patterns, it may be possible to reduce cancer risk through targeted interventions.

Understanding the mechanisms behind these developmental states could lead to breakthroughs in cancer prevention and early detection.

By shifting the focus from genetic mutations to developmental epigenetics, this research challenges existing models of cancer formation.

The findings suggest that cancer prevention strategies could extend beyond traditional approaches, incorporating insights into early developmental processes.

The study provides a foundation for future investigations into how epigenetic states influence cancer risk and offers new hope for early diagnosis and targeted treatments.

The study is published in the journal Nature Cancer.

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