scientists Identify genetic Markers Amplifying Stomach Cancer Risk, Pinpoint Potential New Treatment
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A groundbreaking international study has revealed how the convergence of genetic predispositions, lifestyle factors, and pre-existing conditions dramatically increases the risk of stomach cancer, offering new avenues for early detection and preventative intervention.
Stomach cancer remains a formidable global health challenge, frequently enough diagnosed at late stages when treatment options are limited. Now, researchers from Duke-NUS Medical School, the National University Health System (NUHS) in Singapore, and an international team, have identified a complex interplay of factors that significantly amplify the risk, paving the way for more targeted screening and potential therapies.
The Convergence of Risk Factors
While age, smoking, oral bacteria, and genetic mutations are individually known to contribute to stomach cancer, the new research demonstrates that their combined effect is far greater than the sum of their parts. The study, published in Cancer Discovery, a peer-reviewed journal by the American Association for Cancer Research (AACR), focused on individuals with intestinal metaplasia (IM) – a condition characterized by changes in the stomach lining often linked to chronic inflammation. The team discovered specific genetic alterations, known as SBS17, that are especially prevalent in individuals with IM and are exacerbated by smoking, and IM is more likely to progress.”
The geographically diverse dataset allowed the team to compare genetic changes across populations with varying levels of stomach cancer risk, strengthening the validity of their findings.SBS17, linked to oxidative stress, was also found to be exacerbated by smoking, highlighting the detrimental impact of this lifestyle factor.
A Six-Fold Increase in Risk and the Promise of Early Detection
Previous research by the Singapore Gastric Cancer Consortium (SGCC) in 2023 had already established a six-fold increased risk of stomach cancer in patients with IM. However, the applicability of these findings to populations beyond singapore remained uncertain. This new, international study validates those earlier results, reinforcing IM as a critical pre-cancerous condition.
“Our new results, demonstrated across six countries, reinforce IM as a true pre-cancerous lesion in the development of gastric cancer, and an actionable checkpoint for its prevention,” a senior researcher noted.”The new results also add crucial nuance: IM is heterogeneous and only a subset appears poised to progress.”
This nuanced understanding allows for a more targeted approach to screening and intervention. As a senior consultant with the Division of Gastroenterology and Hepatology at the National University Hospital explained, “now that we know about these, we can aim to use them to identify people who are at high risk and who need closer follow-up. Conversely, we also offer reassurance to people who are at low risk and do not need excessive investigations.”
Unexpected Hope: Repurposing a Common Drug
In a surprising turn, the research team discovered that pyrvinium, a drug currently used to treat intestinal pinworms, may hold promise in slowing the progression of IM. Researchers identified pyrvinium as a potential candidate to inhibit a specific molecular pathway frequently activated in IM. Pre-clinical studies in the US, involving mice and organoids, have shown that pyrvinium suppresses cancer-driving chemical signaling and reverses metaplasia in the stomach.
“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,” a researcher confirmed.
While pyrvinium is already licensed for treating pinworm infections, clinical trials are necessary to determine the appropriate dosage, safety, and efficacy for preventing IM progression. The SGCC is currently preparing to launch these clinical studies, with early-phase trials potentially beginning within one to two years.
Stomach cancer remains a significant threat, claiming between 300 and 500 lives annually in Singapore and ranking among the top 10 causes of cancer-related deaths worldwide. The insidious nature of the disease, often presenting without early symptoms, underscores the importance of proactive screening and preventative measures. This latest research offers a beacon of hope, providing a deeper understanding of the disease’s origins and opening doors to more effective strategies for early detection and intervention.
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