A collaborative research effort involving scientists from the Duke-NUS Medical School and the National University Health System (NUHS) has identified several factors that significantly raise the risk of developing stomach cancer. These findings, published on January 19, 2026, in the journal Cancer Discovery, highlight the roles of genetic mutations, age-related changes in blood cells, smoking, and oral bacteria.
Stomach cancer, also known as gastric cancer, is a major global health concern, being the fifth most common cancer and the fourth leading cause of cancer-related deaths. In 2020, it accounted for approximately 769,000 deaths worldwide. In Singapore, the disease ranks among the top ten causes of cancer-related mortality, claiming around 300 lives annually. Understanding the factors that contribute to this cancer is crucial for developing effective prevention strategies.
Unraveling the Complex Interplay of Risk Factors
The research team, part of the Singapore Gastric Cancer Consortium (SGCC), analyzed over 1,500 intestinal metaplasia samples collected from multiple countries, including collaborators from Hong Kong, Japan, South Korea, Taiwan, and the USA. This extensive dataset allowed the researchers to compare genetic alterations across populations with varying gastric cancer risks.
Through advanced genetic analysis, the team identified 47 significantly mutated genes associated with intestinal metaplasia cells. Notably, mutations in the ARID1A gene correlated with an increased risk of gastric cancer and poorer patient prognosis. Furthermore, a previously unidentified pattern of DNA damage known as SBS17 was found in intestinal metaplasia but absent in healthy stomach tissue. This pattern is linked to oxidative stress, a cellular damage caused by reactive molecules that can be exacerbated by tobacco use.
The discovery that oxidative stress plays a role in the earliest stages of gastric cancer development presents new avenues for intervention. Additionally, the researchers found that pyrvinium, a drug used for treating parasitic infections, could inhibit the growth of intestinal metaplasia cells. Upcoming clinical studies under the SGCC will further explore this potential therapeutic approach.
Link Between Ageing, Genetics, and Bacteria
Another significant finding was the association between clonal hematopoiesis—a process where blood stem cells acquire mutations and proliferate—and increased vulnerability to gastric cancer. This phenomenon is often observed in older adults, which may explain why gastric cancer is frequently diagnosed in this demographic. The study also revealed that individuals with clonal hematopoiesis harbored higher levels of oral bacteria, such as Streptococcus, in their stomachs.
The combination of weakened immunity from clonal hematopoiesis and elevated bacterial levels may promote chronic inflammation, accelerating the progression to gastric cancer.
Professor Patrick Tan, Dean of Duke-NUS Medical School and senior author of the study, emphasized the multifaceted nature of gastric cancer risk, stating, “Gastric cancer is often called a silent killer because it takes hold quietly, long before symptoms appear. What our study shows is that risk does not come from one place—it builds over many years through a complex interplay between ageing, genetic changes, immune shifts, and even the bacteria we carry.”
Co-senior author Professor Yeoh Khay Guan, Chief Executive of NUHS, noted the implications of these findings for patient management. He stated, “Our findings open the door to exploring new and more effective treatments such as eliminating specific bacteria and therapies to inhibit or potentially reverse intestinal metaplasia.”
This research underscores the importance of identifying individuals at high risk for gastric cancer, potentially guiding more focused screening and monitoring efforts.
The study was supported by the Singapore Ministry of Health through the National Medical Research Council (NMRC) and the National Research Foundation (NRF).
As Singapore faces an ageing population, these insights into the biological processes associated with ageing could significantly contribute to the nation’s efforts to promote healthy longevity and resilience.
