Epidemiological evidence suggests that Helicobacter pylori infection is associated with a reduced risk of esophageal adenocarcinoma, the authors explain, but few studies have explored the risk of esophageal cancer according to histology in relation to peptic ulcer disease.

Dr. Shahram Bahmanyar at the Karolinska Institute, Stockholm, Sweden and associates investigated the risk of esophageal cancer by histology among patients hospitalized for gastric ulcer (n= 81,379) or duodenal (n= 61,548) ulcer between 1965 and 2003 in Sweden, compared with the general population.

Patients with duodenal ulcer had a 70% higher risk of esophageal adenocarcinoma than people in the general population, the authors report. Duodenal ulcer was only marginally associated with an increased risk of esophageal squamous cell carcinoma, the results indicate.

In contrast, the researchers note, gastric ulcer was not associated with a significantly increased risk of esophageal adenocarcinoma, but was associated with a significant 80% increased relative risk of esophageal squamous cell carcinoma.

“With due reservations, our finding of a positive association between gastric ulcer and risk of esophageal squamous cell carcinoma adds some further support for the hypothesis that the intragastric environment fostered by corpus atrophy may play a role in esophageal squamous cell carcinoma etiology,” the investigators say.

“This study suggests that the repeatedly confirmed strong inverse relation between H. pylori seropositivity and risk of esophageal adenocarcinoma does not pertain to all infections,” Dr. Bahmanyar and colleagues conclude. “It appears as if the pattern of gastric colonization and/or the clinical consequences in the stomach plays an important role.”

“The new challenge facing us is to clarify the mechanism of the positive association between atrophic gastritis and esophageal squamous cell carcinoma,” writes Dr. Kenneth E. L. McColl from the Western Infirmary, Glasgow, UK in a related editorial.

“This observation supports the hypothesis that it is not H. pylori itself which may influence reflux disease and its complications but the effects of the infection on acid secretion,” Dr. McColl adds.

“Vitamin A may influence gastric carcinogenesis through its essential role in controlling cell proliferation and differentiation,” Dr. Susanna C. Larsson, of Karolinska Institutet, Stockholm, Sweden, and colleagues write. “However, epidemiologic studies of vitamin A, retinol (preformed vitamin A), and provitamin A carotenoids in relation to the risk of gastric cancer have documented inconsistent results.”

In a prospective population-based cohort study of Swedish adults, the researchers examined records of 82,002 Swedish adults who had completed a food-frequency questionnaire in 1997. The subjects were followed through June 2005. Computerized record linkage of the study population to the national and regional Swedish cancer registries was used to ascertain incident cases of gastric cancer.

The mean follow-up was 7.2 years. During that time, a total of 139 incident cases of gastric cancer were diagnosed. The subjects had a mean age at baseline of 61.0 years. Significant inverse associations were observed between intakes of dietary and total vitamin A and retinol and the risk of gastric cancer. A significantly lower risk of gastric cancer was also observed with high intakes of alpha-carotene and beta-carotene.

The multivariate relative risks of gastric cancer comparing the highest with the lowest quartile of intake were 0.53 for total vitamin A (p = 0.02) and 0.56 for total retinol (p = 0.05). The multivariate relative risks for the highest versus the lowest quartiles of intake for alpha-carotene and beta-carotene were 0.50 (p = 0.03) and 0.55 (p = 0.07), respectively. There were no significant associations between beta-cryptoxanthin, lutein, and zeaxanthin, or lycopene intake and gastric cancer risk.

“Significant interactions were found between smoking status and intakes of dietary vitamin A (p = 0.01), total vitamin A (p = 0.01), and alpha-carotene (p = 0.01),” Dr. Larsson and colleagues write. “The associations between vitamin A, retinol, or carotenoid intake and the risk of gastric cancer did not differ significantly across strata of alcohol consumption.”

The results, the authors conclude, “support the hypothesis of a possible protective role of vitamin A in gastric carcinogenesis.”

“As serum biomarkers are useful to detect atrophic gastritis and the location of atrophic lesions (antrum or corpus), it is feasible to carry out the serum test for outpatients who may suffer from gastric cancer, in particular in high-risk areas of gastric cancer,” Dr. Shu Dong Xiao from Shanghai Jiaotong University, China.

Dr. Xiao and colleagues evaluated the use of serum pepsinogen I (PGI), the pepsinogen I/II ratio (PGR), gastrin-17, and Helicobacter pylori-IgG antibodies for screening for atrophic gastritis and gastric cancer in symptomatic patients who had been diagnosed by gastroscopy.

PGI and PGR were significantly decreased in atrophic gastritis and gastric cancer patients, the authors report, compared with healthy controls and patients with gastric or duodenal ulcers.

PGI and PGR levels were lower in atrophic corpus gastritis than in atrophic antral gastritis, the results indicate, and lower in advanced gastric cancer than early stage gastric cancer.

Gastrin-17 level was significantly increased in gastric cancer, without regard to cancer stage, the researchers note. In contrast, gastrin-17 levels were significantly lower in patients with multifocal atrophic gastritis and antral atrophic gastritis than in patients with atrophic corpus gastritis.

All four patient groups (gastritis, cancer, duodenal ulcer, and gastric ulcer) had higher H. pylori positivity rates than the control group, the report indicates.

“Serodiagnosis could be used as a screening method for atrophic gastritis and gastric cancer in large-scale population screening because of its obvious advantages, such as its convenience, relative cheapness, and safety,” the authors conclude.

“If the patient is presenting with alarm symptoms, such as loss of weight, melena, anemia, which are suggestive of gastric malignancy or other GI diseases, endoscopy should be performed without first measuring the serum biomarkers,” Dr. Xiao said.

“We have planned to carry out a research of the healthy subjects over 40 years on whether eradication of H. pylori could prevent the development of gastric cancer in Shanghai,” Dr. Xiao added. “The total number of subjects studied probably would be over 10,000. We will use serum H. pylori IgG antibodies, pepsinogen I and II, and gastrin-17 to pick out those with atrophic gastritis (low serum pepsinogen I and low I/II ratio).”