Stomach Cancer Risk – Highest When Hereditary Factors and Helicobacter Combine

Stomach cancer risk was found to be highest when infection with Helicobacter pylori (H. pylori) combines with certain mutations in genes involved in DNA repair.

H. pylori is a bacterium associated with stomach ulcers and stomach cancer, and half the world’s population is estimated to be infected. However, only a small proportion of infected people will develop stomach cancer.

The Most Comprehensive Study

The Japanese study published in NEJM on 30 March 2023 shows that certain mutations in DNA-repair genes combined with H. pylori infection significantly increase stomach cancer risk. The findings suggest that environmental factors contribute more to hereditary stomach cancer risk than previously thought.

Researchers analyzed samples from 10426 stomach cancer patients and 38153 controls from a Japanese biobank. They first examined the association between germline (inherited) pathogenic mutations in 27 cancer-predisposition genes and stomach cancer. They then calculated the combined effects of pathogenic mutations and H. pylori infection and the overall risk derived from cancer and control samples.

Results

The study is an important step toward reducing H. pylori-associated stomach cancer risk and evaluating early diagnosis and treatment options, particularly in people with inherited alterations. It also highlights that other environmental factors causing DNA damage and contributing to human cancer may have been overlooked. Considering genetic and environmental factors together may therefore help determine stomach cancer risk and prevent disease.

*

More About the Relationship Between H. pylori and Stomach Cancer

H. pylori (Helicobacter pylori) is a spiral-shaped bacterium living in the stomach and upper small intestine. Around half the world’s population is estimated to be infected. Infection is associated with stomach ulcers and stomach cancer.

Although there is no definitive mechanism explaining how H. pylori causes stomach cancer, it is thought to contribute in the following ways:

1. Damage to the stomach lining: H. pylori lives on the gastric mucosa and produces ammonia to neutralize stomach acid. This damages the protective layer and causes inflammation of the stomach wall. Chronic inflammation can eventually cause cell damage and abnormal growth, increasing cancer risk.

2. Reduced stomach acid production: H. pylori infection can reduce stomach acid production, which may damage the gastric mucosa. Low acid levels also allow the growth of other bacteria that contribute to abnormal cell growth and cancer development.

3. Cytokine production: H. pylori releases substances that stimulate the production of inflammation-related proteins called cytokines. These promote inflammation that damages stomach cells and causes abnormal cell growth.

4. Genetic and epigenetic changes: H. pylori infection can cause DNA damage and epigenetic changes in stomach cells. These changes may affect the expression of genes supporting abnormal cell growth and cancer development.

Although stomach cancer risk is not the same for everyone exposed to H. pylori, infection is an important risk factor. Early diagnosis and treatment play an important role in reducing that risk.

How Is H. pylori Diagnosed and Treated?

H. pylori infection is generally diagnosed using the following methods:

1. Urease breath test: This noninvasive test detects urease, an enzyme produced by H. pylori. The patient swallows a urea tablet containing radioactive carbon. If infection is present, urease converts urea into carbon dioxide and ammonia. The carbon dioxide is exhaled, and infection is detected by measuring the proportion of radioactive carbon.

2. Stool antigen test: This detects H. pylori antigens in a stool sample and is highly sensitive and specific for diagnosing infection.

3. Blood test: This measures antibodies produced by the body against H. pylori. It can be used to detect infection but is not suitable for assessing treatment success because antibodies can persist for a while after treatment.

4. Endoscopy and biopsy: Stomach endoscopy can be used to diagnose H. pylori, particularly in patients with upper gastrointestinal symptoms. An endoscope, a thin flexible tube, is passed through the mouth into the stomach, and samples are taken from the stomach wall. Laboratory examination of these samples detects H. pylori.

5. Rapid urease test (CLO test): This detects H. pylori urease in tissue collected during an endoscopic biopsy. The sample is placed in contact with a urea-containing substance; if H. pylori is present, a color change occurs.

How Is H. pylori Treated?

Current treatment generally combines several medicines. These may include antibiotics, acid-suppressing drugs and sometimes gastrointestinal protective agents. Preferred medicines for H. pylori infection include:

1. Proton pump inhibitors (PPIs): These suppress and reduce stomach acid production. Examples include omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole.

2. Antibiotics: Antibiotics eradicate H. pylori. The most commonly used are:

   • Clarithromycin
   • Amoxicillin
   • Metronidazole
   • Tetracycline
   • Levofloxacin

3. H2 receptor antagonists: H2 receptor antagonists are another drug class that suppresses and reduces stomach acid production. Ranitidine and famotidine belong to this group.

4. Gastrointestinal protective agents: These protect the stomach lining and may speed healing. “Sülfakrat” (the source spelling), bismuth subsalicylate and misoprostol are included in this category.

Doctors generally select an H. pylori regimen that may be called “triple therapy” or “quadruple therapy.” Triple therapy consists of a PPI and two antibiotics; quadruple therapy consists of a PPI, two antibiotics and a gastrointestinal protective agent. Treatment generally lasts 10-14 days.

After treatment, doctors perform tests to assess success and determine whether H. pylori has been completely eradicated. If infection persists, they may consider alternative drug combinations and recommend a different regimen.