Every year, approximately 300 to 500 Singaporeans succumb to stomach cancer, which ranks as the city-state’s fourth leading cause of cancer deaths among men and the fifth among women. Without any apparent manifestations in its early stages, stomach cancer is one of the most elusive, hard-to-predict cancers. Upon diagnosis, two out of three patients find themselves grappling with an advanced stage of the disease.

This makes tracking the progression of stomach cancer all the more crucial. A multi-institutional study, conducted by researchers from the National University Hospital (NUH), DUKE-NUS Medical School, National University of Singapore’s Yong Loo Lin School of Medicine and Seoul National University Hospital, has shed light on key genetic factors that enable the early prediction of intestinal metaplasia, a condition linked to heightened risks of developing stomach cancer. This breakthrough points towards a possible paradigm shift for the early detection and management of stomach cancer.

Intestinal metaplasia, characterised by changes in the cells lining the stomach’s mucous membrane, often arises from chronic gastritis or acid reflux. This condition—seemingly benign—harbours a more troubling potential. It serves as an early warning sign of stomach cancer, increasing the patient’s risk of developing the disease by sixfold.

The in-depth study, touted as the largest genomic survey of its kind on intestinal metaplasia, examined over 1,100 tissue samples from a cohort of pre-cancerous patients under the gastric cancer epidemiology programme.

“Employing advanced technologies such as single-cell RNA sequencing and spatial transcriptomics, we pinpointed 26 ‘driver genes’ pivotal in the progression to stomach cancer,”  says Professor Yeoh Khay Guan, Senior Consultant in the Division of Gastroenterology and Hepatology, Department of Medicine, NUH. Prof Yeoh is also the Lead Principal Investigator of the Singapore Gastric Cancer Consortium, a national translational research group that advances stomach cancer research.

This granular analysis, studying genetic material one cell at a time and tracking specific gene expressions, provides a lens into the complex mechanisms through which intestinal metaplasia cells might transform into cancerous ones. Among the key findings is the similarity between certain intestinal stem-like cells in patients with intestinal metaplasia and early-stage stomach cancer cells. This discovery not only offers insight into the potentially malignant trajectory of these cells, but also highlights the critical need for screening to manage stomach cancer effectively.

From refining existing screening protocols to devising more precise treatment and prevention strategies, the study’s findings could be leveraged to stop stomach cancer in its tracks. This is especially relevant in Singapore, where the prevalence of stomach cancer, while demanding attention, does not justify mass screening.

“With this molecular roadmap of disease progression in hand, we are now better positioned to create and implement targeted surveillance and intervention for patients at high risk, as well as explore anti-inflammatory or antibiotic agents to intercept premalignant clones before they evolve into cancer,” says Professor Jimmy So, Head and Senior Consultant in the Division of General Surgery (Upper Gastrointestinal Surgery), Department of Surgery, NUH. “This extends beyond early detection—it’s also about preventing cancer before it takes hold.” 

Integrating genomic data with routine clinical check-ups has already made more accurate stomach cancer predictions a reality. “Simple and inexpensive tests now enable doctors to identify individuals who are at a very high risk of developing stomach cancer,” adds Prof Yeoh, who is also the Chief Executive of the National University Health System (NUHS). “This means we can categorise patients according to their risk profiles, which reduces unnecessary tests and also ensures that they receive the right tests and treatments at the right time.”