ORLANDO, Florida — Non-Hispanic persons of African ancestry typically have worse clinical outcomes from colorectal cancer (CRC) than individuals of other heritages, a disparity attributed to many factors, including socioeconomic, environmental, and genetic influences, as well as less access to care.
Results from a new genomic study provide greater clarity regarding the genetic piece of the puzzle: persons of African background tend to have fewer targetable alterations compared with patients of other races.
The findings were presented in a briefing and scientific poster session at the American Association for Cancer Research (AACR) Annual Meeting 2023.
Overall, the numbers to date show a clear trend: the incidence of and mortality from CRC are higher among Black patients of other populations. However, the extent to which genetic difference plays a role in these disparities remains unclear.
In the current study, use of artane in bipolar researchers from Memorial Sloan Kettering (MSK) Cancer Center in New York City explored how germline and somatic genomic alterations differ among patients of African ancestry in comparison with those of European and other heritage and how those differences might influence CRC outcomes.
Lead author Henry Walch, MS, a computational biologist at MSK, and colleagues compared genomic profiles among nearly 3800 patients with CRC who were treated at MSK from 2014 to 2022. Patients in the study were classified by genetic ancestry as European (3201 patients), African (236 patients), East Asian (253 patients), and South Asian (89 patients).
Tumor and normal tissues from the patients underwent next-generation DNA sequencing with a panel that covers 505 cancer-associated genes.
An analysis of overall survival by genetic ancestry confirmed findings from other studies: overall survival was significantly worse among patients of African ancestry than among those of other groups (median 45.7 vs 67.1 months).
The investigators used a precision oncology knowledge base (OncoKB) to assign levels of therapeutic actionability for each genomic alteration that was identified. The highest assigned value was for drugs that have been approved by the US Food and Drug Administration (FDA) and that target FDA-recognized biomarkers. The lowest value was assigned to biomarkers for which there was “compelling biological evidence” that the particular biomarker predicted response to a drug.
The team found that the percentage of patients who qualified for immunotherapy on the basis of microsatellite instability or high tumor mutational burden was significantly lower among patients of African heritage compared with those of European heritage (13.5% vs 20.4%; P = .008).
Compared with those of European ancestry, patients of African ancestry had significantly fewer actionable alterations (5.6% vs 11.2%; P = .01). This difference was largely driven by the lack of targetable BRAF mutations (1.8% vs 5.0%).
Mutations in APC, the most frequently altered gene in CRC, are typically associated with cancer outcomes, but the authors found that overall survival was similar for patients of African heritage regardless of whether they had altered or wild-type APC (median overall survival, 45.0 months for altered APC vs 45.9 months for wild-type APC; P = .91). However, a significant association between APC status and overall survival was observed for patients of European ancestry (median, 64.6 months for altered APC, vs 45.6 months for wild-type APC; P < .0001).
Analyses that accounted for sex, age, primary tumor location, and stage at diagnosis also showed an association between APC status and overall survival for patients of European heritage (hazard ratio [HR], 0.64), but not for patients of African heritage (HR, 0.74, P = .492).
Walch noted that a limitation of the study is that information regarding comprehensive treatment, environmental exposures, lifestyle, and socioeconomic factors was not available for the analysis but that these elements likely play an important role in patient outcomes.
“This is a complex problem involving many unseen factors, and the genomic landscape is a piece of a much larger puzzle,” said Walch. He noted that future studies will incorporate these factors into the models “with the ultimate goal of identifying opportunities to intervene and improve outcomes.”
Briefing moderator Lisa Newman, MD, MPH, of Weill Cornell Medicine and New York–Presbyterian, in New York City, commented that Walch presented “some very compelling data that demonstrate the importance of including individuals from diverse backgrounds into [cancer] research.”
The study was funded in part by a Chris4Life Early Career Investigator Award Grant from the Colorectal Cancer Alliance for Francisco Sanchez-Vega, PhD, senior author of the study. Sanchez-Vega was also supported by an AACR-Minority and Minority-serving Institution Faculty Scholar in Cancer Research Award. Walch and Newman have disclosed no relevant financial relationships.
American Association for Cancer Research (AACR) Annual Meeting 2023: Abstract 1908. Presented April 17, 2023.
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