Serum pepsinogen 1 and anti‐Helicobacter pylori IgG antibodies as predictors of gastric cancer risk in Finnish males

Summary Background Serum pepsinogen 1 (SPG1) and anti‐ Helicobacter pylori serology have been used for gastric risk stratification in Asia. Aim To assess utility of these markers in a Western population. Methods SPG1 measurements were available for 21 895 Finnish male smokers in the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention Study. We used Cox proportional hazards models adjusted for potential confounders to estimate gastric cancer hazard ratios ( HR ) and 95% confidence intervals (95% CI ) for low SPG1 (<25 μg/L). In a subset (n = 3555) with anti‐ H. pylori serology, these markers jointly defined the following: Group A ( H. pylori [−], SPG1 [normal]; reference group), Group B ( H. pylori [+], SPG1 [normal]), Group C ( H. pylori [+], SPG1 [low]) and Group D ( H. pylori [−], SPG1 [low]). Odds ratios ( OR s) and 95% CI were calculated using multivariate logistic regression. Results There were 329 gastric cancers diagnosed an average of 13.9 years after baseline. Pre‐diagnostic low SPG1 was significantly associated with increased gastric cancer risk ( HR 2.68, 95% CI 1.99‐3.61). Among subjects with both SPG1 and H. pylori serology, groups B, C and D had increased gastric cancer OR s (95% CI ) of 1.79 (1.21‐2.64), 3.85 (2.36‐6.28) and 6.35 (2.20‐18.34), respectively. CagA seropositives had significantly higher OR s than CagA seronegatives within group B ( P heterogeneity = 0.01). For groups B and C, repeat SPG1 level at 3 years did not further stratify gastric cancer risk. Conclusions Low SPG1 was associated with increased gastric cancer risk in our large Finnish cohort. A single measurement of SPG1 along with H. pylori whole cell and CagA serology provides potentially useful prediction of gastric cancer risk.