Utilizing AACR Project GENIE to Research Cancer Disparities

An early-career investigator uses GENIE data to examine genomic differences in early-onset colorectal cancer among different racial groups.

Black Americans have higher incidence and mortality rates from colorectal cancer than any other racial group in the United States. New research released at the AACR Annual Meeting 2021 found that in colorectal cancer patients under age 50, genetic alterations varied by race, which could help pave the way to understanding more about the disparity.

A study led by Andreana Holowatyj, PhD, MS, of the Vanderbilt-Ingram Cancer Center in Nashville examined disparities in early-onset colorectal cancer by exploring somatic mutations among patients from different racial groups. Early-onset colorectal cancer is defined as the detection of the disease in patients under the age of 50.

“This first-of-its-kind study revealed molecular differences in early-onset colorectal cancer by race,” said Dr. Holowatyj, an assistant professor of Medicine and Cancer Biology at the Vanderbilt University School of Medicine. “Although validation is needed, these findings may help us understand if molecular features of the tumor contribute to disparities in disease burden.”

Dr. Holowatyj’s research was presented at a session highlighting how data from AACR Project GENIE—a publicly accessible international cancer registry of real-world data assembled through data sharing between 19 of the leading cancer centers—is advancing cancer research.

With the release of the ninth data set in February 2021, the GENIE registry hit a milestone of samples sequenced from over 100,000 patients, making it one of the largest fully public cancer genomic data sets in the world. Vanderbilt University was one of the founding members of the GENIE consortium.

In 2019, Dr. Holowatyj was recognized a NextGen Star. The AACR NextGen Stars program provides opportunities and visibility for early-career scientists at the AACR Annual Meeting.

Three years later she considers her presentation at AACR Annual Meeting 2021 to be a one-of-a-kind opportunity.

“The AACR is a leader in the field of oncology research,” she said. “To be able to be part of the AACR’s national and international platform is a unique opportunity to showcase the work that my team is doing and really forge new collaborations with investigators all across the field and all around the world.”

Although most of the work for this recent study was performed in a dry lab—i.e., on the computer—Dr. Holowatyj also spends a lot of time at the laboratory bench, or wet lab. As both an epidemiologist and a molecular biologist, she equates the dual specialty with an approach she thinks is reflected in the well-known TV and book series “The Magic School Bus.”

“I just always use that term, ‘I take a Magic School Bus approach,’” Holowatyj said. “You jump from taking findings at the society level, and then you’re really jumping into what’s going on at the cellular level.”

Her desire to connect cells and society is a big part of what fuels her passion to address cancer disparities.

For Dr. Holowatyj and her research team, Project GENIE was key to exploring whether underlying biological factors may be contributing to her observations from a previous study that found Black patients with early-onset colorectal cancer had a greater risk of death compared to white patients of the same age with the disease.

“The information found within the AACR Project GENIE database, which includes clinical-grade genomic sequencing data and other clinical data from around the world, provided us with sufficient cases to study this disease across diverse populations in a way that we would not be able to at individual institutions,” Dr. Holowatyj said.

She and her colleagues examined tumor mutations by race in patients with early-onset colorectal cancer. While they found no differences in tumor mutational burden between white and Asian/Pacific Islander patients under age 50 with the disease, their analysis revealed that Black patients had significantly higher tumor mutational burden than white patients. Furthermore, distinct genetic mutations were observed among patients of different races.

Dr. Holowatyj and colleagues published their final report in AACR’s journal Cancer Discovery in March 2023. According to an accompanying commentary by three experts at Yale University, “The findings shed light on a deeper understanding of complex biological and genetic mechanisms for colorectal cancer in diverse populations.”

Dr. Holowatyj said her research may have long-term implications within the context of precision medicine.

“Ultimately, we’re looking at individual patients diagnosed with colorectal cancer and trying to discern what makes the tumor in one individual or one population subgroup unique from others,” she explained. “By doing this and understanding the differences that diverse populations may present with, the hope is that we can tailor future therapeutic targets and future prevention strategies for specific population subgroups.”

The AACR Cancer Disparities Progress Report 2020 details how the limited knowledge of cancer biology in racial and ethnic minorities diminishes the potential of precision medicine in certain populations and highlights how AACR Project GENIE data is helping to change that by providing more information about cancer in all populations.

Dr. Holowatyj also pointed out that cancer health disparities are about more than just biology.

“While this study revealed potential biological determinants of disparities in early-onset colorectal cancer, it is important to acknowledge that race is a social construct and this is just one piece of the puzzle,” Dr. Holowatyj noted. “Several complex and related factors, including genetic ancestry and systemic racism, also may contribute to such disparities.

“Cancer doesn’t take into account your race, sexual orientation, political affiliation, or other social construct,” she added. “Cancer is a disease that affects everyone. It’s only right that we work toward mitigating disease disparities across all populations and reduce the disease burden for everyone. It is a privilege to get to do this every day.”

Special thanks to Donn Jones and other members of the News and Communications staff at the Vanderbilt University Medical Center (VUMC) for help in acquiring the visuals for this story.

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