Identification of genetic drivers for esophageal cancer creates new opportunity for screening, treatment

Esophageal adenocarcinoma (EAC) is a highly lethal cancer, with a five-year survival rate of less than 20 percent. Although a precursor lesion to EAC, called Barrett's esophagus (BE), is present in roughly seven percent of middle-aged adults, less than one percent of BE patients will progress to EAC, making it difficult to determine which individuals are at risk of developing this deadly cancer.

Their results, published in Gastroenterology, highlight that nine percent of EAC patients harbor mutations in cancer-predisposing genes, shedding light on the causes of progression to the disease and new possibilities for screening and treatment.

This

Gfx-Study was based on genomic data from 640 individuals with EAC, pooled from public U.S. and U.K.databases

5GFX-59 % had highly rare, cancer-predisposing germline mutations, most commonly in the ATM gene

To validate these results, the researchers also

• GFX-Analyzed nearly 300 individuals from MGH cohorts who either had EAC or BE with high-grade dysplasia (a precursor to EAC)

• BE without cancer progression after 10 or more years

Again, they found that germline mutations, especially in the ATM gene, were the most prevalent in EAC patients, with evidence that in people who progressed to EAC, there may be additional epigenetic changes that cause abnormalities in ATM expression compared to non-progressors.

Results from the study also shed light on the existing question of

GFX-why approximately 30% of EAC patients do not have a common cancer-causing mutation?

EAC patients without TP53 mutations in their tumors were instead much more likely to have pathogenic germline mutations, and at a rate comparable to that of ovarian cancer, which is known to be a highly genetics-dependent disease

Reference: Identification of genetic drivers for esophageal cancer creates new opportunity for screening, treatment; Gastroenterology, DOI: 10.1053/j.gastro.2023.07.015