Research News

After reporting a promising connection between genetics and immunity in colorectal cancer, Cleveland Clinic researchers Stephanie Schmit, PhD, MPH, and Ya-Yu Tsai, PhD, knew their 2023 publication was only a starting point. They needed to make sure the same association would apply more broadly. 

In their new study published in Gastroenterology, Drs. Tsai and Schmit moved beyond their initial 5,400-person analysis to design an expanded replication study. They analyzed genetic data from more than 180,000 people across the world.  

By analyzing an external replication dataset, the team asked whether the same biological relationship between genetic variability affecting the immune system and cancer risk could be observed in a different and much larger population.  

Seeing consistent patterns at scale helped researchers strengthen their hypothesis. Their conclusions held true across datasets: Across the world, individuals with more genetic variation in their immune systems had immune systems that were better at recognizing, targeting and fighting colorectal cancer. The new publication’s findings extended further, linking immune variation to cancer risk and survival. 

"It’s important to test whether we see consistent patterns as study populations scale in size and scope. That’s how we learn which findings apply to which people, and which findings are robust enough to build on,” Dr. Tsai says. 

Validating their initial conclusions in new contexts demonstrated a critical step for any researcher who wants to make sure their research has a broad impact. In the Schmit Lab’s case, knowing their findings aren't limited to a small group means they can work toward improving risk assessment and personalized care based on which genetic features a patient inherited from their parents. 

Global scaling shows the bigger picture 

Smaller studies with similar research participants can be imprecise. It’s not uncommon for an interesting finding to either become stronger or to disappear when you look beyond any individual group. It’s also possible to miss things entirely. 

This is why the Schmit Lab increased their sample size by almost twenty times and expanded the scope of their project to include people from all over the world. They could ask whether their results were consistent across populations and contexts, not just within the initial group studied in 2023. 

The Schmit Lab’s scientific rigor is increasingly important in biomedical research, where early findings don’t always show a final truth. By testing their original question again on a global scale, the Schmit Lab showed their study could be repeated and replicated, which strengthened confidence in an interesting observation.  

"Repeating and expanding studies helps us see which findings are relevant in which populations,” Dr. Schmit says. “That’s a critical step toward translating research insights into more personalized approaches to disease prevention and care for patients."