SINGAPORE, Feb 7 — A Singapore study has found that age, smoking, oral bacteria and genetic mutations can combine to amplify the risk of stomach cancer.

The Straits Times reported that scientists from Duke‑NUS Medical School and the National University Health System (NUHS), working with international researchers, identified early biological changes in the stomach lining that precede cancer.

“It is about finding the right people, at the right time, with the right interventions before cancer takes hold,” said Professor Yeoh Khay Guan, chief executive of NUHS and co‑senior author of the study.

The study, published in Cancer Discovery, a journal of the American Association for Cancer Research, highlighted red flags in patients with intestinal metaplasia (IM), a condition linked to chronic gastritis or acid reflux.

Researchers analysed more than 1,500 samples across six countries and identified 47 significantly mutated genes in IM cells.

They found that loss of the tumour suppressor gene ARID1A, age‑related blood mutations and a DNA damage pattern known as SBS17 increase the risk of gastric cancer and worsen prognosis.

“ARID1A stands out because it provides crucial growth control and is the second most frequently mutated driver gene in gastric cancer, occurring in 17 to 27 per cent of cases,” said Professor Patrick Tan, dean of Duke‑NUS Medical School and co‑senior author.

He added that when ARID1A is lost, the stomach’s protective safeguards are weakened and IM is more likely to progress.

The scientists found that SBS17, a DNA damage pattern linked to oxidative stress, is further aggravated by smoking.

Yeoh said the findings can help doctors identify people at high risk who need closer follow‑up, while reassuring those at low risk.

Stomach cancer, also known as gastric cancer, is among the world’s deadliest cancers because it often shows no symptoms in the early stages, leading to late diagnosis.

It is one of the top 10 causes of cancer‑related deaths and claims between 300 and 500 lives annually in Singapore.

The Singapore Gastric Cancer Consortium (SGCC), a national research programme, has been studying pre‑cancerous patients since 2007 using advanced genetic technologies.

In 2023, SGCC researchers found that patients with IM face a six‑fold increased risk of developing stomach cancer.

“That study, however, was confined to Singapore patients, and it was unclear how generalisable our findings were and if they could be extended to other countries. For findings to have true clinical value, international validation is required, preferably across multiple countries,” according to Yeoh.

Yeoh said the new international study validates IM as a true pre‑cancerous lesion and an actionable checkpoint for prevention.

The team also discovered that pyrvinium, a drug used to treat pinworm infections, can slow the growth and transformation of stomach lining cells into IM cells.

“Our colleagues in the US have also performed pre‑clinical studies in mice and organoids, and (found) that pyrvinium suppresses cancer‑driving chemical signalling and reverses metaplasia in the stomach,” Yeoh said.

He added that clinical trials are needed to establish dosage, safety and efficacy for pyrvinium in slowing or preventing IM progression.

SGCC is now embarking on clinical studies to test pyrvinium’s effect, with early‑phase trials expected to take one to two years if approved.