The study, published in the Proceedings of the National Academy of Sciences (PNAS), which involved highly advanced genetic sequencing, brings in essential knowledge that will allow researchers to develop future therapies to specifically target these newly identified mutations.
“This milestone study builds on our previous genetic research on colorectal cancer,” study author Sanford Markowitz, MD, PhD, principal investigator of the federal gastrointestinal cancers research program (GI SPORE), said in a news release. ”It illustrates the extraordinary impact that dedicated, collaborative teams can make when they combine scientific experience and ingenuity with significant investment.”
The GI SPORE program began in 2011 and is one of the few existent in the country, and includes disease studies in minority patients.
There has always existed a discrepancy between colorectal cancer rates in African Americans and other populations, with 46.8 cases for every 100,000 African Americans, and 38.1 cases for every 100,000 Caucasian Americans.
However, the reason behind these rates was never completely understood by scientists.
“These advancements underscore the importance of university-based research,” Congresswoman Marcia L. Fudge, former chair of the Congressional Black Caucus and representative of the 11th district, which includes Case Western Reserve and UH Case Medical Center, stated. “I am proud that researchers from Northeast Ohio are taking meaningful steps toward identifying pathways to block a devastating disease that disproportionately affects members of the African American community.”
From the initial stages of research, Dr. Markowitz and colleagues always suspected there was a genetic reason behind the observed discrepancies.
“Identifying gene mutations has been the basis of all the new drugs that have been developed to treat cancer in the last decade,” Dr. Markowitz explained. “Many of the new cancer drugs on the market today were developed to target specific genes in which mutations were discovered to cause specific cancers.”
“We wondered if colon cancer is the same disease molecularly in African Americans individuals as it is in Caucasian individuals. Or could colon cancer be the same disease behaving differently in one population compared to another,” added study author Joseph E. Willis, MD, associate professor of pathology, Case Western Reserve School of Medicine, director of tissue management, Case Comprehensive Cancer Center, and Vice Chair of Pathology for Clinical Affairs at UH Case Medical Center. “This study gave us our answer. Colon cancer in African American patients is a different disease molecularly.”
Researchers sequenced DNA from 103 colorectal cancer samples derived from African American patients and compared it with 129 colorectal cancer samples from Caucasian patients, analyzing 50 million bits of data from a total of 20,000 genes. This allowed them to find 20 new genetic mutations in cancer samples from African Americans, with 15 of these mutations specifically affecting this patient population. Furthermore, all of these mutations were 3.3-fold more frequent in African American tumors than in cancer samples from Caucasians.
In particular, two genes, EPHA6 and FLCN, were found mutated exclusively in African American samples, with 5.8% (EPHA6) and 2.91% (FLCN) of colorectal cancers carrying these genetic alterations.
“This is the first study to perform a comprehensive gene mutation characterization and comparison of these colorectal cancer tumors in two ethnicities – African American and Caucasian,” lead author Kishore Guda, DVM, PhD, assistant professor, General Medical Sciences (Oncology), Case Comprehensive Cancer Center said in the news release. “Our next step will be to collaborate with other centers in investigating African American populations in different regions of the United States to determine whether they also share the unique gene signature found in the Cleveland African American community.”