Unraveling the Genetic Underpinnings of Gastric Cancer in Hispanic/Latino Patients

Dr. Hwang and a group of external collaborators found that Hispanic/Latino gastric cancer patients exhibit a higher incidence of CDH1 mutations, which may explain some of the observed racial disparities in disease incidence.

05/06/2020

A collaborative team led by Lerner Research Institute and University of Texas Southwestern Medical Center researchers have uncovered genetic susceptibilities that put Hispanic/Latino patients at greater risk for developing gastric cancer than African American, Asian and White patients.

Gastric (stomach) cancer—sometimes more technically referred to as gastric adenocarcinoma—develops in the lining of the stomach and is the second leading cause of cancer-related deaths worldwide. This type of cancer, however, does not afflict patient groups equally.

More Hispanic/Latino patients are diagnosed with gastric cancer than any other patient group and typically have worse cancer-related outcomes. Additionally, gastric cancer often presents earlier among Hispanic/Latino patients and with distinct clinicopathological features.

Published in Cancer Research, the research team—co-led by Tae Hyun Hwang, PhD, Department of Quantitative Health Sciences, and Sam Wang, MD, and Matthew Porembka, MD, both from the Department of Surgery, University of Texas Southwestern Medical Center—found distinct genetic and tumor characteristics that may contribute to increased disease risk among this patient population.

They sequenced genetic material from 83 Hispanic/Latino gastric cancer patients and compared the genomic and tumor profiles to those from Asian and White patients collected and analyzed as part of the Cancer Genome Atlas (a cancer genomics initiative led by the National Cancer Institute). Drs. Hwang, Wang and Porembka identified seven mutations of interest among the Hispanic/Latino group, but one in particular stood out.

Hispanic/Latino patients, they found, had a higher incidence of germline mutations (those that can have a hereditary component) in the CDH1 gene. CDH1 (cadherin 1) encodes the instructions to produce a protein called epithelial cadherin, which is found abundantly in the cells that line body surfaces and cavities, like the stomach. They also found that gastric tumors from Hispanic/Latino patients were more commonly genetically stable molecular subtype—that is, they had lower mutation frequencies—than in other patients, indicating worse prognosis.

Dr. Hwang noted that while multiple factors must be considered, and are like at play, when narrowing in on the causes of increased disease incidence—including socioeconomic and environmental risk factors—this study into biological risk factors is important.

“Currently, the biological basis of why Hispanic/Latino patients more often develop gastric cancer has not been explained, or really even investigated thoroughly,” he said. “Relatively few large-scare genomic efforts aimed at understanding gastric cancer pathologies and disparities have included this patient population. This analysis will help to begin filling some critical gaps in knowledge.”

As Dr. Hwang alludes, more research will be important to investigate mechanistically how CDH1 may give rise to gastric cancer in Hispanic/Latino patients, but their findings offer important insights that should be considered for genetic screening and counseling. With additional study, knowledge that a Hispanic/Latino patient has the CHD1 mutation may one day inform not just earlier diagnosis, but also patient-specific treatment options.



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