Decoding the Genetic Factors of Stomach Cancer Development


A recent study published in Cancer Cell has made a breakthrough in understanding the genetic factors involved in the development of stomach cancer. The researchers focused on intestinal metaplasia, a condition that increases the risk of stomach cancer. This condition often goes unnoticed or presents mild symptoms in its early stages, making it difficult to detect.

Stomach cancer is a significant health concern globally, and in Singapore, it ranks as the fourth leading cause of cancer deaths in men and the fifth among women. Late detection is a major issue, with two-thirds of stomach cancer patients being diagnosed at an advanced stage. The study, which is the largest genomic survey of patients with intestinal metaplasia to date, analyzed over 1,100 tissue samples using advanced technologies such as single-cell RNA sequencing and spatial transcriptomics.

The researchers identified 26 “driver genes” that play a crucial role in the transition from intestinal metaplasia to stomach cancer. This groundbreaking finding provides insights into the mechanisms underlying this transformation and paves the way for early detection and targeted prevention strategies.

The advancements in DNA sequencing allowed researchers to uncover various cell populations within the stomach changes associated with intestinal metaplasia. This understanding of the “ticking mechanism” of a time bomb, as described by Dr. Huang Kie Kyon, one of the study’s co-first authors, offers valuable insights into the potential transformation of these cells into cancerous cells, influenced by various factors.

According to Professor Patrick Tan, the Senior Vice-Dean for Research at Duke-NUS Medical School and a member of the research team, the comprehensive dataset assembled in this study provides unparalleled insights into the progression of cell changes in the stomach leading to cancer. By combining clinical information with genetic data from advanced molecular technologies, researchers can better predict which stomach conditions may progress to stomach cancer. This knowledge can aid in the development of more precise preventive measures.

The study was a collaborative effort involving researchers from Duke-NUS, the National University Hospital (NUH), the National University of Singapore’s Yong Loo Lin School of Medicine (NUS Medicine), and the Seoul National University Hospital. The research demonstrates the strength of Singapore’s multi-institutional cancer research ecosystem and its global collaborations.

The findings of the study have implications for clinical practice. The researchers discovered that a specific subpopulation of intestinal stem-like cells in patients with intestinal metaplasia closely resembles early stomach cancer cells, suggesting an early origin and the potential for malignancy. Screening for intestinal metaplasia becomes crucial in managing stomach cancer risk.

Professor Jimmy So, one of the co-senior authors of the study and Head & Senior Consultant of the Division of General Surgery (Upper Gastrointestinal Surgery) at NUH, emphasized the clinical implications of the research. He suggested that the molecular roadmap of disease progression from intestinal metaplasia opens up opportunities for targeted surveillance of high-risk patients and the use of anti-inflammatory or antibiotic agents to intercept premalignant clones before they evolve into cancer. This approach could significantly improve patient outcomes through early detection.

On a population level, the study may lead to more efficient screening strategies and better allocation of resources to intercept gastric cancer development in high-risk individuals. This is particularly relevant for countries like Singapore, where the incidence of stomach cancer is moderate compared to Japan and South Korea, where mass screening is warranted due to high incidence rates.

The researchers found that combining genomic data with clinical check-ups enhances the accuracy of stomach cancer predictions. Genetic tests, including simple and inexpensive blood tests, can be used to identify individuals at a high risk of developing stomach cancer. By dividing people into risk groups, healthcare resources can be directed to those who need them the most. This approach can potentially save resources and ensure that high-risk individuals receive the necessary tests and care.

1. Source: Coherent Market Insights, Public sources, Desk research
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