January 12, 2015
2 min read

Novel gene mutations associated with CRC in black patients identified

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Researchers have identified new genetic mutations that are unique to colorectal cancers in black patients, who have higher incidence and mortality compared with other populations.

“This milestone study builds on our previous genetic research on colorectal cancer,” Sanford Markowitz, MD, PhD, Ingalls professor of cancer genetics at Case Western Reserve School of Medicine and medical oncologist at University Hospitals Case Medical Center, said in a press release. “It illustrates the extraordinary impact that dedicated, collaborative teams can make when they combine scientific experience and ingenuity with significant investment.”

Sanford Markowitz, MD, PhD

Sanford Markowitz

As part of the $11.3 million federal gastrointestinal cancers research program (GI SPORE), according to the release, Markowitz and colleagues used whole-exome and targeted DNA sequencing to evaluate somatic mutations in 103 CRC samples from black patients compared with 129 CRC samples from white patients treated at UH Case Medical Center in Cleveland. Overall, they examined 50 million bits of data from 20,000 genes in every cancer, the release said.

“We wondered if colon cancer is the same disease molecularly in African-American individuals as it is in Caucasian individuals. Or could colon cancer be the same disease behaving differently in one population compared to another,” Joseph E. Willis, MD, associate professor of pathology at Case Western Reserve School of Medicine, director of tissue management at Case Comprehensive Cancer Center and vice chair of pathology for clinical affairs at UH Case Medical Center, said in the release. “This study gave us our answer. Colon cancer in African-American patients is a different disease molecularly.”

Joseph E. Willis, MD

Joseph E. Willis

The investigators identified 20 new genes in the black CRC samples that were significantly mutated (P<.05). To test whether these genes are preferentially targeted for mutations in black vs. white CRCs, they resequenced them in the white samples and found an estimated twofold overall increase in the number of mutations per tumor in black vs. white patients (P<.001), which was driven by the 3.3-fold increase in mutations for the top 15 genes preferentially affecting the black patients.

Two genes were of particular interest because they were mutated exclusively in black CRCs and belonged to known oncogenic pathways. Mutations in EPHA6 were detected in 5.8% of the black CRCs compared with none of the white CRCs and were significantly associated with black ethnicity (P=.007). Mutations in FLCN were detected in 2.91% of the black CRCs compared with none of the white CRCs and were associated with black ethnicity (P=.086). Mutations in the top 15 genes accounted for 41% of cancers in the black patients compared with 15% of the white patients.

“This is the first study to perform a comprehensive gene mutation characterization and comparison of these [CRC] tumors in two ethnicities,” Kishore Guda, DVM, PhD, assistant professor of general medical sciences at Case Comprehensive Cancer Center, said in the 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.”

Kishore Guda, DVM, PhD

Kishore Guda

“We are eager to explore and pinpoint [CRC]-causing gene mutations, as the first step to improving outcomes, and hopefully someday to saving lives, among African-American patients affected by this illness,” Markowitz said.

Disclosure: The researchers report no relevant financial disclosures.