Reframing genetic predisposition through DDT exposure research
Author: Sam Cormier
The EPA outlawed use of DDT in 1972 because of the synthetic pesticide’s potential risk to human health and destructive environmental effects.
Nearly 50 years later, Professor Sonia de Assis of Georgetown’s Lombardi Comprehensive Cancer Center is studying DDT as a model to understand how environmental toxins pose deleterious effects over multiple generations. Innovative work by her research team is changing the way we think about how the environment affects our genes, including predisposition to cancer and other diseases.
Dr. de Assis is focused on epigenetic inheritance of disease, the idea that environmental factors leave molecular marks in the parents’ germline. That “molecular memory” of past toxic exposures can be transmitted—independent of DNA—to the next generation and affect their predisposition to disease.
“While family history is an important risk factor for many diseases, not all familial susceptibility can be explained by genetics,” she said. “There might be another way by which disease predisposition can be passed between generations.”
Her latest project won a prestigious R01 Grant from the National Institutes of Health. This paved the way for an expanded inquiry into how paternal exposures to environmental toxins such as DDT can change a group of molecules called non-coding RNAs in sperm and lead to abnormal development in offspring. The work, initiated as a preliminary investigation with funding from the GEI Impact Program, has produced findings that show children of fathers exposed to DDT have increased rates of cancer and diabetes.
Those efforts have developed into cutting-edge research exploring how environmentally induced epigenetic inheritance occurs. Using DDT as an example, Dr. de Assis is examining how environmental information including toxins gets coded in sperm and how that information affects the first stages of fetal development after conception, causing predisposition for diseases.
There’s a strong social justice component to Dr. de Assis’ work.
“Poorer and more disadvantaged communities are more prone to being exposed to environmental toxicants than wealthier communities,” she said. “These communities are being affected now, but the next generation might also be affected. If we are aware of that, we can try to break the cycle.”
Different ethnic groups experience a higher prevalence of certain diseases, including cancer. African Americans, for example, have the highest death rate and shortest survival of any racial and ethnic group in the US for most cancers. More than that, she said, the “molecular memory of our parents’ environmental exposure can program us to have worse outcomes for diseases.”
Part of the work’s novelty is its focus on the paternal role in epigenetics, a field where research tends to focus more on the way environmental factors are passed from mothers to offspring.
Conditions like diabetes and obesity in fathers can alter the RNA of sperm, affecting fetal development. Dr. de Assis hopes that identifying how these paternal factors affect development will lead to improved care for the would-be father prior to conception.
Growing up in Brazil, Dr. de Assis spent her early years on a farm, always “very curious about the natural world.” Her old neighborhood in the Brazilian city of Goiânia is similar to disadvantaged communities in the U.S. affected by pollution and other environmental toxins.
Dr. de Assis’ research seeks to identify the intergenerational genetic causes of disease in hopes of improving how we approach and treat those conditions. By bringing epigenetics to the field of oncology, her team highlights the value of a holistic approach that combines environmental and medical research. It’s a strong reflection of the core Georgetown Jesuit value of cura personalis, a Latin phrase that refers to care of the whole person.