Age, smoking, bacteria, genetic mutations together can raise risk of stomach cancer: Singapore study
Stomach cancer remains a significant global health threat, often diagnosed late due to a lack of early symptoms. However, new research is offering a more nuanced understanding of the factors that contribute to its development, and potentially, how to identify those at highest risk before the disease progresses.
Unraveling the Complexities of Stomach Cancer Risk
Scientists have long known that factors like age, smoking, oral bacteria, and genetic mutations can individually increase the risk of stomach cancer. A recent study, however, reveals that the combination of these factors dramatically amplifies that risk. This discovery, stemming from collaboration between Duke-NUS Medical School, the National University Health System (NUHS), and an international team of researchers, focuses on the earliest biological changes occurring in the stomach lining.
Identifying High-Risk Individuals
The research, published in Cancer Discovery, centres on a condition called intestinal metaplasia (IM). IM involves changes in the stomach’s mucous lining, often occurring in individuals with chronic gastritis or acid reflux. Researchers analyzed over 1,500 tissue samples from six countries, identifying 47 significantly mutated genes in cells with IM.
Specific genetic changes, including the loss of the tumor suppressor gene ARID1A – found in 17 to 27 percent of gastric cancer cases – age-related blood mutations in stem cells, and a particular pattern of DNA damage known as SBS17, were linked to increased cancer risk and poorer outcomes. The large, geographically diverse dataset allowed for comparisons across populations with varying levels of stomach cancer risk.
The Role of Specific Genes and Lifestyle Factors
According to Professor Patrick Tan, dean of Duke-NUS Medical School, not all genes have the same impact. “ARID1A stands out because it provides crucial growth control,” he explained. The study also found that SBS17, linked to oxidative stress, can be exacerbated by smoking.
“It is about finding the right people, at the right time, with the right interventions before cancer takes hold,” stated Professor Yeoh Khay Guan, chief executive of NUHS. The goal is to identify those at high risk for closer monitoring, while reassuring those at low risk and avoiding unnecessary investigations.
What’s Next? A Potential New Avenue for Prevention
Researchers have unexpectedly discovered that pyrvinium, a drug currently used to treat intestinal pinworms, may slow the growth and transformation of stomach lining cells into those associated with intestinal-type IM. Pre-clinical studies in mice and organoids suggest pyrvinium suppresses cancer-driving chemical signaling and reverses metaplasia in the stomach.
However, pyrvinium is currently only licensed for pinworm infections. Clinical trials are needed to determine appropriate dosage, safety, and efficacy for preventing IM progression. The Singapore Gastric Cancer Consortium (SGCC) is already planning such studies, with early-phase trials potentially beginning within one to two years.
Frequently Asked Questions
What is intestinal metaplasia (IM)?
Intestinal metaplasia is a condition where changes occur in the mucous lining of the stomach, often seen in patients with chronic gastritis or acid reflux.
Which gene was highlighted as particularly important in the study?
The ARID1A gene was highlighted as crucial because it provides growth control and is frequently mutated in gastric cancer, occurring in 17 to 27 percent of cases.
Could a drug already approved for another condition potentially help prevent stomach cancer?
Researchers discovered that pyrvinium, a drug used to treat intestinal pinworms, may slow the growth and transformation of stomach lining cells into those that cause cancer, but clinical trials are needed to confirm its effectiveness and safety for this purpose.
As research continues, will a more targeted approach to stomach cancer prevention become a reality for those at highest risk?