Nasty H pylori packs up and heads east

Sharp declines in Europe are matched by rises in Japan so large they strain the healthcare system

By Brian Hoyle

Helicobacter pylori is now recognized as infecting the stomach of up to 80% of the world's population. For most, the infection is innocuous. But the infection can cause stomach ulcers and, even more ominously, has been linked to the development of gastric cancer.

In Japan, about 60 million people harbour the microbe in their stomachs. The prevalence of a particularly nasty strain translates into rates of gastritis and peptic ulcers, and gastric cancers that are among the highest in the world. Indeed, H pylori infections are straining the Japanese healthcare system, according to Dr Masanori Hatakeyama, a molecular oncologist at Hokkaido University in Sapporo.

The nasty H pylori strains pack their punch courtesy of a gene, designated CagA. The gene encodes a protein (CagA, or vacuolating cytotoxin) that directs a multi-pronged attack at the host. It wrecks the functioning of gastric epithelial cells, blocks the normal immune activity of B-lymphocytes, making it easier for H pylori to gain an infectious foothold. Worse still, it inhibits the build-up of tumour suppressor p53 in the stomach epithelial cells, leading to mucosa-associated lymphoid tissue lymphoma. And, if that's not enough, Dr Hatakeyama's research has implicated CagA in the phosphorylation-activated over stimulation of a signaling pathway, which fuels abnormal gastric cell growth and preludes gastric adenocarcinoma.

ANTIBIOTIC ASSAULT
Research presented several weeks ago at the joint meeting of the American Association for Cancer Research and the Japanese Cancer Association described the occurrence of CagA in almost all East Asian H pylori isolates that Dr Hatakeyama and his colleagues examined. Genetic variations in Cag,A, detected in different East Asian populations, mirrored variations in the incidence of gastric cancer.

Furthermore, "the predominant CagA proteins isolated in East Asia have a distinct sequence, " says Dr Hatakeyama. If the implied connection between critical CagA sequences and the development of gastric cancer bears out, then the sequences could become a powerful tool in assessing the clinical outcome of infection.

That said, since other virulence factors can contribute to stomach cancer, selective eradication of CagA-positive strains is not sufficient protection. Rather, an all-out antibiotic assault would be needed. In the Far East, where most strains are CagA-positive, antibiotic use has merit, says Arnoud van Vlief of the Esasmus MC-University Medical Center, Rotterdam, Netherlands.

Antibiotic use would not be justified in Europe, where CagA-positive strains are less frequent, and would only encourage development of resistance, according to Dr van Vlief. His opinion is backed up by results of a study published in the February issue of Annals of Oncology. Examination of gastric cancer-related mortality in 25 European countries from 1950 to 1999, revealed a steady fall in the mortality rate. From 1980 to 1999, the decline was dramatic: approximately 50% in European Union countries, 45 percent in Eastern Europe, and 40% in Russia. Steady declines in mortality in younger and middle aged people bode well for the future.

The roots of the bright European picture are not known. Improvements in diet and food quality, recognition of H pylori and use of control schemes, and perhaps swifter and more accurate detection all likely have played a role.