SINGAPORE – While it is well-known that age, smoking, oral bacteria and genetic mutations can individually cause stomach cancer, a recent study has found that when they occur together in one person, the risk is amplified.

This discovery by scientists from Duke-NUS Medical School and the National University Health System (NUHS), together with an international team of researchers, provides a peek into the earliest biological changes in the stomach lining that precede the cancer and allow doctors to identify those at high risk.

“It is about finding the right people, at the right time, with the right interventions before cancer takes hold,” Professor Yeoh Khay Guan, chief executive of National University Health System (NUHS) and co-senior author of the study, told The Straits Times.

Published in Cancer Discovery, a monthly peer-reviewed scientific journal by the American Association for Cancer Research (AACR), the study highlighted several red flags in people with intestinal metaplasia (IM), a condition where there are changes in the mucous lining of the stomach in patients with chronic gastritis or acid reflux.

Using advanced genetic analyses, the researchers identified 47 significantly mutated genes in IM cells after analysing more than 1,500 samples collected across six countries.

Mutated genes, including the loss of a key tumour suppressor gene called ARID1A, age-related blood mutations in stem cells as people grow older, and a distinct pattern of DNA damage known as SBS17 result in an increased risk of gastric cancer and poorer prognosis.

This large, geographically diverse dataset enabled the team to compare genetic changes across populations with differing levels of stomach cancer risk.

Speaking to ST, Professor Patrick Tan, dean of the Duke-NUS Medical School and co-senior author of the study, said genes are not equal in their effects.

“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. ...when AR...