Publication Date
4-18-2024
Journal
Scientific Reports
DOI
10.1038/s41598-024-59257-3
PMID
38637560
PMCID
PMC11026501
PubMedCentral® Posted Date
4-18-2024
PubMedCentral® Full Text Version
Post-Print
Published Open-Access
yes
Keywords
Female, Humans, Male, Adenocarcinoma, Esophageal Neoplasms, Mutation, Black or African American, White, Exome Sequencing, Cancer, Genetics, Gastroenterology
Abstract
Esophageal adenocarcinoma is the most common histological subtype of esophageal cancer in Western countries and shows poor prognosis with rapid growth. EAC is characterized by a strong male predominance and racial disparity. EAC is up to fivefold more common among Whites than Blacks, yet Black patients with EAC have poorer survival rates. The racial disparity remains largely unknown, and there is limited knowledge of mutations in EAC regarding racial disparities. We used whole-exome sequencing to show somatic mutation profiles derived from tumor samples from 18 EAC male patients. We identified three molecular subgroups based on the pre-defined esophageal cancer-specific mutational signatures. Group 1 is associated with age and NTHL1 deficiency-related signatures. Group 2 occurs primarily in Black patients and is associated with signatures related to DNA damage from oxidative stress and NTHL1 deficiency-related signatures. Group 3 is associated with defective homologous recombination-based DNA often caused by BRCA mutation in White patients. We observed significantly mutated race related genes (LCE2B in Black, SDR39U1 in White) were (q-value < 0.1). Our findings underscore the possibility of distinct molecular mutation patterns in EAC among different races. Further studies are needed to validate our findings, which could contribute to precision medicine in EAC.
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Digestive System Diseases Commons, Gastroenterology Commons, Medical Genetics Commons, Oncology Commons, Public Health Commons
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