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 levels in GC but not in controls are correlated with the rise in intragastric pH, indicating that excessive gastrin release in GC is affected by lower intragastric pH. 3. Serum gastrin level and CagA seropositivity are significantly increased in the majority of GC patients, and are the only variables in multivariable analysis to have a predominant influence on GC formation, which suggests that both these parameters may be implicated in H. pylori-related gastric carcinogenesis. 4. H. pylori-infected GC patients produce significantly more IL-8 than do non-GC controls, probably reflecting CagA-positive H. pylori-associated gastritis.
Konturek
S J
SJ
Dept of Physiology, University Medical School, Cracow, Poland.
Starzynska
T
T
Konturek
P C
PC
Karczewska
E
E
Marlicz
K
K
Lawniczak
M
M
Jaroszewicz-Heigelman
H
H
Bielanski
W
W
Hartwich
A
A
Ziemniak
A
A
Hahn
E G
EG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000032:analysis*; D001426:Bacterial Proteins / Q000032:analysis*; D004415:Dyspepsia / Q000150:complications / Q000382:microbiology / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000097:blood*; D016481:Helicobacter Infections / Q000150:complications* / Q000175:diagnosis; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000503:physiopathology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D005755:Gastrins; D007074:Immunoglobulin G; D016209:Interleukin-8; C080866:cagA protein, Helicobacter pylori