Health x Wellness
Understanding Early Risks: Scientists Link Ageing, Smoking, and Oral Bacteria to Stomach Cancer
Scientists at Duke-NUS Medical School and the National University Health System (NUHS) have uncovered a complex “web” of factors that significantly increase the risk of stomach (gastric) cancer.
The research identifies a unique interplay between genetic mutations, age-related blood shifts, and even oral bacteria in the stomach, offering new ways to identify high-risk individuals before the disease develops.
The study, published in Cancer Discovery, analysed more than 1,500 intestinal metaplasia samples across six countries, including Singapore, Japan, and South Korea. Gastric cancer is the fourth leading cause of cancer-related deaths globally and remains a “silent killer” because it develops over decades, often starting with chronic inflammation in the stomach lining.
The Biological Path to Cancer
Stomach cancer typically progresses through a series of stages, starting with chronic inflammation that leads to intestinal metaplasia—a condition where normal stomach cells convert into cells that resemble those found in the intestines.
Key findings from the genetic analysis of these metaplastic cells include:
- The ARID1A Gene: Mutations in this specific gene were found to be associated with an increased risk of gastric cancer and a poorer prognosis.
- The SBS17 DNA Signature: Researchers identified a distinct pattern of DNA damage known as SBS17 in intestinal metaplasia. This pattern is linked to oxidative stress, a type of cellular damage that is significantly worsened by tobacco smoking.
The Ageing and Microbial Connection
The study also shed light on why stomach cancer is more prevalent in older populations. The team discovered that clonal hematopoiesis—a process where ageing blood stem cells acquire mutations and multiply—is associated with a higher susceptibility to gastric cancer.
Interestingly, individuals with these age-related blood mutations also showed:
- Weakened Immunity: Clonal hematopoiesis may weaken the immune system’s ability to keep inflammation in check.
- Bacterial Overgrowth: These individuals carried higher levels of oral bacteria, specifically Streptococcus, in their stomachs.
This “dual-impact” of compromised immunity and increased bacterial presence is believed to fuel the chronic inflammation that accelerates the progression to cancer.
New Avenues for Prevention
The discovery of these markers provides clinicians with a potential roadmap for earlier, more precise screening. “These findings point to new ways to identify individuals at highest risk… opening opportunities for targeted prevention and precise screening,” the researchers noted.
One promising therapeutic avenue discovered during the study involves pyrvinium, a drug currently used to treat parasites. The researchers found that pyrvinium was able to inhibit the growth of intestinal metaplasia cells, and future clinical studies are being planned to explore its potential in potentially reversing these early precancerous changes.
“Gastric cancer is often called a silent killer because it takes hold quietly,” said Professor Patrick Tan, Dean at Duke-NUS Medical School. “Our study shows that risk does not come from one place—it builds over many years through a complex interplay between ageing, genetic changes, immune shifts and even the bacteria we carry”.
