Ethnic disparities in cancer can be driven by many factors – from social determinants of health to the effects of racism, economic inequality, or genetics. Esophageal adenocarcinoma (EAC) is a cancer that is often preceded by Barrett’s esophagus (BE) and affects the mucus-secreting glands of the lower esophagus, but the cellular progression from BE to EAC is poorly understood. Previous research investigating ethnic disparity in EAC has found that Black people are four- to five-fold less likely to develop EAC than White people (1).
Now, researchers from the University of California San Diego School of Medicine have used artificial intelligence-guided tools to investigate ethnicity-influenced drivers of EAC initiation and progression, which were validated with human organoid models, patient-derived biopsies of BE, a cross-sectional study of patients with BE and EAC, and a genomics study of BE progression (2). The results confirmed that all EACs must develop from BE and highlighted a CXCL8/IL8↔neutrophil immune microenvironment behind the cellular transformation of EACs. This driver was absent in African Americans, but was prominent in White participants; risk of EAC progression was also associated with absolute neutrophil count and network-derived gene signatures. The finding that the immune microenvironment is significantly induced in White participants compared with African Americans suggests that the inflammatory microenvironment is likely a key driver – which would explain the significant discrepancy in EAC risk.
“This neutrophil driver was prominent in Caucasians, but notably absent in African Americans,” said study author Debashis Sahoo (3). “Conversely, SNPs associated with ethnic changes in absolute neutrophil count, such as benign ethnic neutropenia characterized by lower numbers of neutrophils but no increased risk of infection, are common in persons of African ancestry and may act as a deterrent to prevent BE from becoming EAC.”
Another study investigated the intrinsic link between ethnicity and prostate cancer, which has significant geo-ethnic disparity (4). Researchers at the University of Sydney sequenced the genomes of 183 treatment-naïve ancestrally and globally distinct prostate cancer patients to generate a large cancer genomics resource for sub-Saharan Africa that identified around two million somatic variants. Not only did those with African ancestry have notably elevated tumor mutational burden, the researchers also reported an increase in genome alterations, predicted damaging mutations, and mutational signatures.
The findings demonstrate the effectiveness of using larger genomic datasets of geo-ethnically diverse populations to identify rarer, restricted subtypes of prostate cancer. The researchers hope that, eventually, these methods will be used to study multiple types of cancer and perhaps even develop more personalized predictions, prognoses, and prevention pathways that factor a person’s ethnicity into their cancer risk.
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References
- AP Thrift, HB El-Serag, Clin Gastroenterol Hepatol, 14, 330 (2016). PMID: 26528803.
- P Ghosh et al., JCI Insight, 7, e161334 (2022). PMID: 36134663.
- University of California San Diego (2022). Available at: https://bit.ly/3ywVIr9.
- W Jaratlerdsiri et al., Nature, 609, 552 (2022). PMID: 36045292.