HELICOBACTER-PYLORI, PEPSINOGEN, AND RISK FOR GASTRIC ADENOCARCINOMA

The objective of this project was to determine the association of Heli cobacter pylori infection and serum pepsinogen levels on subsequent ri sk for gastric adenocarcinoma. This nested case-control study was set in a large health maintenance organization. One hundred thirty-six cas es of gastric adenocarcinoma and 136 matched controls without adenocar cinoma from a large cohort that had contributed serum in the 1960's we re studied. The presence of IgG against H. pylori had previously been determined by enzyme-linked immunosorbent assay. Serum levels of pepsi nogens I and II were ascertained by radioimmunoassay. In a sample of s ubjects, the presence of antiparietal cell antibodies was determined b y immunofluorescent antibody assay (Nichols Laboratory). There were 98 cases of adenocarcinoma of the antrum, body, or fundus (distal cancer s) and 30 of the cardia or gastroesophageal junction (proximal cancers ). By univariate analysis, H. pylori infection [odds ratio (OR), 3.6; P < 0.001] and serum pepsinogen I < 50 ng/ml (OR = 2.9; P = 0.003) wer e both associated with development of distal cancer. In multivariate a nalysis, there was interaction between the two variables; H. pylori in the absence of low pepsinogen I was independently associated with can cer (OR, 2.4; P = 0.04) but low pepsinogen I in the absence of H. pylo ri infection was not associated with cancer (OR, 0.8; P > 0.5). In com bination, however, H. pylori infection and a low pepsinogen I were ass ociated with a marked increase in the risk of developing distal malign ancy (OR, 10.0; P = 0.08). Low serum pepsinogen I with H. pylori infec tion but not in its absence is associated with a increased risk for di stal gastric cancer. This suggests that infection rather than gastric atrophy is the determining factor in cancer risk.