by Delthia Ricks , Medical Xpress

Credit: Pixabay/CC0 Public Domain

In 1982, two Australian physician–scientists discovered a spiral-shaped bacterium whose form not only dictated its function, but its capacity to dwell in the human body’s harshest chemical environment would help identify it as the cause of serious afflictions of the stomach, including cancer.

Drs. Barry Marshall and Robin Warren shared the 2005 Nobel Prize in medicine for their discovery of Helicobacter pylori and their additional finding that H. pylori is the cause of stomach ulcers. H. pylori’s corkscrew shape and long flagella help the pathogen work its way into the mucus lining of the stomach where it flourishes.

Marshall drank a broth of the bacteria in an act of daring self-experimentation, proving in 1984 that H. pylori causes gastritis and peptic ulcers. Based on that finding, antibiotics became an overnight cure. Subsequent research worldwide confirmed the pathogen’s link to cancer.

Now, decades after H. pylori’s discovery, medical scientists at the National Taiwan University College of Medicine wanted to know if a fecal screening test that spots the presence of H. pylori could serve as an early warning signal of stomach cancer. They designed a study to screen people on a massive community-wide scale with the hope of aiding in the reduction of stomach cancer incidence and mortality.

While stomach cancer isn’t a leading cause of cancer incidence and death in the United States or Europe, it is a major cause of cancer and mortality throughout Asia, including Japan. In India, a new center named in honor of Marshall was opened last month because of the problematic incidence of H. pylori disorders there.

Globally, H. pylori-linked adenocarcinoma of the stomach ranks as the third leading cause of cancer with an estimated 800,000 new cases annually, according to the World Health Organization.

Working with a team of researchers from the College of Medicine, Dr. Yi-Chia Lee, lead author of a study published in the JAMA, invited tens of thousands of residents in Taiwan—152,503 people in all—to participate in the screening project.

Also known as gastric cancer, an estimated 90% of cases worldwide are directly tied to H. pylori infection. The bacteria are also the underlying cause of yet another malignancy, a form of lymphoma known as MALT, which stands for mucosa-associated lymphoid tissue. MALT was not a target in the study.

Lee and colleagues hypothesized going into the research that their analysis would determine if screening by way of an H. pylori stool antigen test, HPSA, along with a fecal immunochemical test, also known as FIT, was superior to, about the same, or lesser than FIT alone. FIT tests are designed to screen for colon cancer by identifying occult blood in fecal samples. FIT screening, although not designed to detect upper gastrointestinal malignancies, has been effective in identifying adenocarcinoma of the stomach.

“Helicobacter pylori is a contributing factor to the development of gastric cancer, and bacterial eradication treatment may prevent its occurrence,” writes Lee, describing what is more frequently called antibiotic combination therapy. Just as antibiotic therapy became the treatment standard for peptic ulcers following Marshall’s groundbreaking discovery, the drugs are also the medications of choice for H. pylori inflammatory conditions that lead to cancer.

To avoid antibiotic resistance, the treatment generally involves triple-drug antibiotic therapy along with a proton pump inhibitor, or PPI. The latter lowers stomach acid. Identifying people at risk of stomach cancer through screening and prescribing combination therapy essentially stops the malignancy before it starts, researchers associated with the study say.

“Whether community screening for H. pylori can reduce rates of gastric cancer, or gastric cancer mortality remains unknown,” added Lee, who specializes in internal medicine.

The team contacted residents of Changhua County, Taiwan who were between the ages of 50 and 69, inviting them to take part in the study. Participants were invited to participate in 2014, the year screening began. Recruitment continued until 2018. The team randomized 63,508 residents to screen with HPSA and FIT together, and 88,995 for screening with FIT alone. The current JAMA study marked the final assessments in the years-long research.

H. pylori is tricky as a screening target because at least half the world’s population unwittingly carries the bacteria and never develops gastritis, ulcers or stomach cancer. But for those who are susceptible because of genetics, diet, environment or all three, the infection can cause chronic inflammation.

The bacteria thrive in the stomach’s mucus layer because they secrete an enzyme called urease, which protects colonies from destruction by harsh stomach acid. Urease breaks down the stomach’s urea into neutral ammonia, rendering the pathogens’ microenvironment alkaline and conducive to survival.

Chronic inflammation caused by colonies of H. pylori can lead to precancerous changes in the stomach, which is the reason combination therapy was part of the study. H. pylori has been designated a Class 1 carcinogen by the International Agency for Research on Cancer, a division of WHO. A Class 1 designation means there is sufficient evidence that the designated agent causes cancer. Other Class 1 carcinogens include cigarette smoke and UV radiation, according to the IARC.

But despite years of data collection, the research produced mixed results, underscoring that targeting H. pylori through the HPSA test did not add much to the overall results. For example, the team recorded a gastric cancer incidence rate of 0.032% in the HPSA and FIT combined screening group compared with a 0.037% incidence rate in the group that was tested only with FIT screening. In terms of mortality, the data showed a 0.015% rate for the combination test screening group compared with 0.013% for those who were screened by FIT alone.

“Among residents of Taiwan, an invitation to test for HPSA combined with FIT did not reduce rates of gastric cancer or gastric cancer mortality, compared with an invitation for FIT alone,” Lee and the team concluded. “However, when differences in screening participation and length of follow-up were accounted for, gastric cancer incidence, but not gastric cancer mortality, was lower in the HSPA with FIT group, compared with FIT alone.”

More information: M. Constanza Camargo, Fecal Immunochemical Test and Helicobacter pylori Stool Antigen Co-Testing, JAMA (2024). DOI: 10.1001/jama.2024.8611

Journal information: Journal of the American Medical Association

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