Helicobacter pylori and CagA Status, Serum Gastrin, Interleukin-8 and Gastric Acid Secretion in Gastric Cancer

Background: Despite numerous epidemiological studies, the association between Helicobacter pylori infection and gastric cancer (GC) remains unexplained. This study was designed to determine the seropositivity of H. pylori and cytotoxin-associated gene A (CagA), serum gastrin and interleukin-8 (IL-8) levels as well as basal intragastric pH and maximal histamine-induced gastric acid outputs (MAO) in a large series of GC patients and controls. Methods: 337 GC patients (118 men and 219 women; median age 59.4; range 21-87) and 337 controls randomized for sex and age entered the study. Serum IgG antibodies to H. pylori and CagA and serum levels of IL-8 were measured by enzyme-linked immunosorbent assay, while serum-amidated gastrin was determined by specific radioimmunoassay and correlated with gastric luminal pH. Results: The numbers of GC patients and controls involved in the study in various age groups, ranging from 20 to >70 years, were similar, but overall H. pylori IgG seropositivity in GC patients was significantly higher (90.8%) than in controls (79.2%). The overall CagA seropositivity in GC patients was about double (58.2%) that in controls (25.2%). Serum gastrin levels over the calculated cut-off value (38.88 pM/L) were found in several-fold larger number in GC patients (48%) than in controls (8.3%) and, similarly, serum IL-8 values over the cut-off point (1.77 pg/mL) occurred in almost all (99.7%) GC patients but in only a few controls (0.3%). Basal intragastric pH above the cut-off point (pH = 4.50) was observed in about 58.2% of GC patients compared to 15.1% in controls, and strong correlation between the serum gastrin and gastric pH was found in GC but weak in controls. The cut-off value for MAO was 12.3 mml/h; MAO below this cut-off value occurred in 89.9% of GC patients and in only 4.7% of controls. A summary odds ratio (SOR) in GC for H. pylori IgG was 2.59 (95% Cl; 1.61-4.22) for CagA - 4.12 (95% Cl; 2.93-5.8), for serum gastrin - 10.25 (95%; 6.47-16.47) and for MAO - 15.2 (95% Cl; 9.45-39.82). Multivariable analysis of serum gastrin, IgG and CagA, and luminal pH and MAO values revealed that only gastrin and CagA have significant influence on GC formation (OR >1 in logistic regression). Conclusions: 1. CG patients show significantly higher H. pylori IgG and CagA seropositivity than dyspeptic age- and gender-matched controls, confirming that gastric infection with CagA expressing H. pylori greatly increases the risk of GC. 2. Serum gastrin level