Molecular Characterization of Esophageal Adenocarcinomas and Factors Influencing Racial Differences in Incidence

Barrett"s Esophagus;Esophageal Cancer;Racial Disparities;Esophageal Adenocarcinoma;Oncology and Hematology;Health Sciences;Cancer Biology

Ferrer-Torres, DayshaWang, Thomas D ;

University of Michigan

关键词: Barrett";    s Esophagus;    Esophageal Cancer;    Racial Disparities;    Esophageal Adenocarcinoma;    Oncology and Hematology;    Health Sciences;    Cancer Biology;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/138728/dferrert_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

The incidence of esophageal adenocarcinoma (EAC) has been rising at an alarming rate over the past three decades (>450-fold). Identification of patients with the metaplastic condition termed Barrett’s esophagus (BE), is a risk factor for the development of EAC, yet allows patients to undergo endoscopic surveillance biopsy to help detect cancer. Our group and others have identified markers that can potentially identify high-grade dysplasia (HGD) and/or EAC in BE patients. However, we have observed that >30% of patients with cancers at the gastroesophageal junction (GEJ) have no previous history of BE. These cancers are also similarly increasing in incidence thus new approaches are also needed for these patients. Interestingly, the increasing incidence of EAC primarily affects the Caucasian population as compared to the African American (AA) population. Therefore, in this thesis we aim to understand: 1) whether EAC vs. tumors located at the GEJ are molecularly distinct, 2a) the characterization of molecular events at the transcriptome level associated with the progression from non-dysplastic BE to dysplasia to cancer 2b) as well as biomarkers that identify patients that are at greatest risk for development of EAC and 3) understanding the basis for the difference in the incidence of EAC between CAU and AA. We were able to show that EAC and GEJAC tumors are molecularly similar, and identified cell surface markers that can be used to detect both non-BE derived GEJs and EACs. Using transcriptional analysis of BE, dysplasia, and EAC we identified splicing has a key dysregulated pathway in BE progression. In addition, we observed an increase in the ATM/DNA-response damage in this progression that, we assume, is associated with loss of protective mucins. Importantly, we have identified a novel genomic event that reduces the expression of the detoxifying enzyme GSTT2 in the esophagus of Cau populations as compared to AA populations. This body of work adds to our understanding of molecular events in EAC and GEJ and could potentially impact the way we diagnose and treat these cancers in the future.