Which is the most important risk factor for gastric cancer?

• A. Chronic NSAIDs
• B. Pernicious anemia
• C. Family history
• D. H. pylori infection

Answer: (D)

Chronic Helicobacter pylori infection is the strongest risk factor for gastric cancer because it drives long-standing inflammation of the stomach lining, setting off a stepwise progression from chronic gastritis to atrophic gastritis, to intestinal metaplasia, then dysplasia, and finally intestinal-type gastric adenocarcinoma. This inflammation creates a environment with genetic and epigenetic changes that push the mucosa toward cancer, and eradicating the infection can reduce future risk.

Pernicious anemia can raise risk through autoimmune atrophic gastritis and metaplastic changes, but it’s less common and its impact is smaller compared with the pervasive effect of H. pylori infection. Family history also increases risk, reflecting genetic and environmental factors, but it doesn’t reach the same level of risk as persistent infection. Chronic NSAID use is not a primary driver of gastric cancer and is more linked to ulcer risk than to cancer risk in this context.