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

SUMMARY

Background

Serum pepsinogen (SPG) 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

SPGI 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 SPGI (<25μg/l). In a subset (n=3,555) with anti- H. pylori serology, these markers jointly defined the following: Group A ( H. pylori[−], SPGI[normal]; reference group), Group B ( H. pylori[+], SPGI[normal]), Group C ( H. pylori[+], SPGI[low]) and Group D ( H. pylori[−], SPGI[low]). Odds ratios (ORs) and 95% CI were calculated using multivariate logistic regression.

Results

There were 329 gastric cancers diagnosed an average of 13.9 years after baseline. Prediagnostic low SPGI was significantly associated with increased gastric cancer risk (HR 2.68, 95% CI 1.99–3.61). Among subjects with both SPGI and H. pylori serology, groups B, C and D had increased gastric cancer ORs (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 ORs than CagA seronegatives within group B ( P _{heterogeneity} =0.01). For groups B and C, repeat SPGI level at 3 years did not further stratify gastric cancer risk.

Conclusions

Low SPGI was associated with increased gastric cancer risk in our large Finnish cohort. A single measurement of SPGI along with H. pylori whole cell and CagA serology provides potentially useful prediction of gastric cancer risk.