Which of the following is least directly associated with an increased risk of gastric cancer: pernicious anemia, H. pylori (Helicobacter pylori) infection, linitis plastica, or peptic ulcer disease?

Linitis Plastica is the Least Directly Associated with Gastric Cancer Risk

Peptic ulcer is the least directly associated with an increased risk of gastric cancer among the listed conditions.

Analysis of Risk Factors for Gastric Cancer

Pernicious Anemia

• Pernicious anemia is strongly associated with gastric cancer development through its relationship with chronic atrophic gastritis 1
• Patients with pernicious anemia are recognized as a high-risk group for gastric cancer, warranting specific referral guidelines for upper GI cancer evaluation 1
• The condition is listed as a known risk factor that should prompt investigation when combined with dyspepsia 1

H. pylori Infection

• H. pylori is the most consistent and well-established risk factor for gastric cancer 1
• The infection increases gastric cancer risk by approximately 2.5-fold, with some studies showing up to 6-fold increased risk 1
• H. pylori causes persistent active gastritis that may progress to atrophic gastritis, intestinal metaplasia, and eventually gastric cancer 1
• Eradication of H. pylori infection is considered the most promising strategy to reduce gastric cancer incidence 1

Linitis Plastica

• Linitis plastica is not a precursor to gastric cancer but rather a specific form of diffuse-type gastric adenocarcinoma characterized by rigid, thickened stomach walls 1
• It represents an advanced manifestation of gastric cancer itself rather than a risk factor for developing gastric cancer 1

Peptic Ulcer Disease

• The relationship between peptic ulcer disease and gastric cancer is complex and varies by ulcer location 2
• Duodenal ulcers are actually associated with a reduced risk of gastric cancer (standardized incidence ratio of 0.6) 2
• While gastric ulcers show some association with gastric cancer risk, this relationship is less direct than the other conditions listed 2, 3
• The association between peptic ulcer disease and gastric cancer is largely mediated through their common association with H. pylori infection rather than being an independent risk factor 4, 5

Clinical Implications

• H. pylori eradication is recommended to prevent gastric cancer development, particularly before preneoplastic conditions develop 1
• Patients with pernicious anemia should be considered for gastric cancer screening due to their elevated risk 1
• The test-and-treat strategy for H. pylori is recommended for patients with dyspepsia without alarm symptoms 5
• Endoscopy is warranted for patients with alarm symptoms or those at high risk for gastric cancer 1

Common Pitfalls in Risk Assessment

• Failing to distinguish between gastric and duodenal ulcers when assessing gastric cancer risk 2
• Not recognizing that linitis plastica is a manifestation of gastric cancer rather than a risk factor 1
• Overlooking the protective association between duodenal ulcers and gastric cancer 2, 3
• Assuming all peptic ulcer disease increases gastric cancer risk, when the relationship depends on ulcer location and other factors 4, 2