News Release

Gene variation may be early indicator for gastric cancer

A University of Arizona Health Sciences study identified a gene variation that could inform clinicians which patients are more susceptible to developing stomach cancer.

Peer-Reviewed Publication

University of Arizona Health Sciences

TUCSON, Arizona — Researchers at the University of Arizona Health Sciences are hoping to catch stomach cancer before it develops in at-risk patients. In a paper published in Gastroenterology, researchers identified a genetic variation that could help identify when patients with Helicobacter pylori are more likely to develop stomach cancer. 

The National Cancer Institute cites infection with H. pylori as the primary identified cause of certain types of stomach cancer. H. pylori is a bacterium that grows in the mucosa, or membrane layer that lines the stomach.

“This study is proposing that if you are carrying this particular allele, you are more likely to have an aggressive type of response to the bacteria that can result in complications,” said the study’s senior author, Juanita L. Merchant, MD, PhD, Regents Professor of Medicine and chief of the Division of Gastroenterology at the UArizona College of Medicine – Tucson.

In the United States, H. pylori is more prevalent in Hispanics, African Americans and the elderly. Dr. Merchant cited data suggesting that 1-3% of people with H. pylori will develop gastric cancer and that the cure rate is around 30%, which is low compared with some other types of cancer. 

Current diagnosis of stomach or gastric cancer requires the patient to undergo an upper endoscopy, where a doctor looks for signs of cancer and takes a tissue sample for analysis. 

For years, Dr. Merchant and colleagues have been investigating new ways to diagnose stomach cancer in its earliest possible stages. In 2020, they published research on a promising biomarker identified through a simple blood test that appears in some patients before stomach cancer develops.

The new study focused on the molecular pathways that control the activation of immune cells in response to H. pylori infection, specifically the action of toll-like receptor 9 (TLR9).

Located within immune cells, TLR9 signals the immune system when to fight an infection. However, H. pylori infection can constantly trigger TLR9 activation over long periods of time, leading to the chronic inflammation. The long-term presence of inflammation caused by H. pylori infection is believed to be one of the triggers for cancer developing in the stomach. 

“This addresses the question of what role the immune microenvironment has in gastric cancer,” said Dr. Merchant, who is a research member of the UArizona Cancer Center. “We have shown that these immune cells do play an important role.”

Researchers found that the chronic activation of TLR9 in the stomach triggers a series of events that includes increased production of interferon α, a signaling protein that can change the genetic signature of specialized immune cells known as myeloid-derived suppressor cells, or MDSCs. Prior research has linked MDSCs with H. pylori infection.

Dr. Merchant and her team focused on each step of the pathway and identified a specific genetic change – allele rs5743836 TLR9 minor C – that was linked to higher levels of TLR9 and interferon α and a greater incidence of gastric tumors. The allele is a single nucleotide polymorphism, or SNP, which is a genetic change in the DNA between genes. 

“Because TLR9 and the SNP can be tested by DNA, they could be used as biomarkers to help us identify which patient populations are going to be more susceptible to the cellular changes that might lead to cancer based on their genetic background,” Dr. Merchant explained. “Those are the patients who could benefit from increased endoscopic surveillance.”

Eventually, the findings may also lead to new therapeutic options for patients.
“We have previously found a real-time biomarker in a blood test, and now we have something we can see in DNA,” Dr. Merchant said. “Our next step is to look at therapy options.”

# # #

About the University of Arizona Health Sciences
Located on campuses in Tucson, Phoenix and Gilbert, Ariz., the University of Arizona Health Sciences is one of the top-ranked academic medical centers in the southwestern United States. UArizona Health Sciences includes the College of Medicine – Phoenix, College of Medicine – Tucson, College of Nursing, Mel and Enid Zuckerman College of Public Health, R. Ken Coit College of Pharmacy, and Health Sciences Global and Online. In addition, 15 UArizona Health Sciences centers and programs focus on cancer, neurodegenerative diseases, pain and addiction, and respiratory diseases; biomedical informatics, health technology innovation and simulation training; and health disparities, precision health care and treatments, and pandemic preparedness. A leader in next-generation education, research, clinical care and public outreach, UArizona Health Sciences employs nearly 5,000 people, has approximately 4,000 students and 900 faculty members, and garners more than $220 million in research grants and contracts annually. For more information: (Follow us: Facebook | Twitter | YouTube | LinkedIn | Instagram).

About the University of Arizona Cancer Center
The University of Arizona Cancer Center is the only National Cancer Institute-designated Comprehensive Cancer Center with headquarters in Arizona. The UArizona Cancer Center is supported by NCI Cancer Center Support Grant No. CA023074. With its primary location at the University of Arizona in Tucson, the Cancer Center has more than a dozen research and education offices throughout the state, with more than 300 physicians and scientists working together to prevent and cure cancer. For more information: (Follow us: Facebook | Twitter | YouTube).

About the University of Arizona College of Medicine – Tucson
The University of Arizona College of Medicine – Tucson is shaping the future of medicine through state-of-the-art medical education programs, groundbreaking research and advancements in patient care in Arizona and beyond. Founded in 1967, the college boasts more than 50 years of innovation, ranking among the top medical schools in the nation for research and primary care. Through the university's partnership with Banner Health, one of the largest nonprofit health-care systems in the country, the college is leading the way in academic medicine. For more information: (Follow us: Facebook | Twitter | LinkedIn | Instagram).


Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.