Role of bacterial and genetic factors in gastric cancer in Costa Rica.
OBJECTIVE
To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR).


METHODS
According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes.


RESULTS
Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4).


CONCLUSIONS
Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica.
Con
Sergio A
SA
Centro Digestivo Doctores Con-Mediplaza, Pavas 245-1200, San José, Costa Rica. scon@gastrocolon.com
Takeuchi
Hiroaki
H
Con-Chin
Gil R
GR
Con-Chin
Vicky G
VG
Yasuda
Nobufumi
N
Con-Wong
Reinaldo
R
D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D003364:Costa Rica / Q000453:epidemiology; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D005798:Genes, Bacterial; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017472:Receptors, Interleukin-1 / Q000235:genetics; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology*; D055815:Young Adult
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C508609:IL10 protein, human; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; D016753:Interleukin-10