The relationship between Helicobacter pylori infection, the virulence genotypes of the infecting strain and gastric cancer in the African setting.
BACKGROUND
The relationship between Helicobacter pylori infection and gastric carcinoma remains controversial, especially in the African setting where infection is common, while gastric cancer is perceived to be uncommon, the basis of the so called 'African enigma'. This discrepancy between infection and the development of disease is commonly attributed to differences in host, environment and bacterial factors. Interest in the bacterial factors has focused on heterogeneity in the so-called 'virulence genes'.


OBJECTIVE
The aim of this prospective, case-controlled study was to establish whether H. pylori infection is significantly associated with gastric cancer and to investigate whether gastric cancer is associated with genotypically distinct (as it relates to the candidate virulence genes) organisms in this population.


METHODS
Patients with histologically confirmed gastric cancer were matched with nonulcer dyspeptic controls for age (within 5 years), gender and ethnicity. Helicobacter pylori status was determined by RUT, histology, culture and serology (locally validated and used as default determinant of H. pylori status). Tumors were classified according to the Lauren classification. The 'virulence genotype' of 17 paired culture samples was determined by previously described and validated molecular techniques (cagA presence, vacA alleles, structure of the cag pathogenicity island and analysis of the iceA alleles). Categorical variables were analysed by the chi2 test.


RESULTS
Forty-eight patients (median age 59 years) could be adequately matched to controls. 39/48 (81%) cases and 43/48 (90%) controls were H. pylori positive (NS). Significant differences in the virulence genotypes of infecting strains were noted: vacAs2-controls 24%, cases 0%, p < .00001; vacAs1 present - cases 100%, controls 76%, p < .05; cagA-3'-length > 650 bp - cases 47%, controls 0%, p < .002; cag pathogenicity island intact - cases 82%, controls 43%, p < .04; iceA1 - cases 53%, controls 6%, p < .005. cagA was found in all subjects.


CONCLUSIONS
This study indicates that, in this African population at least, there is no difference in the prevalence of H. pylori infection when comparing gastric cancer cases with matched controls. However, the findings suggest that gastric cancer may be associated with infection by organisms that are genotypically different from those not associated with disease.
Louw
J A
JA
Gastrointestinal Clinic, Department of Medicine, University of Cape Town, Groote Schuur and Red Cross War Memorial Hospitals, Cape Town, South Africa.
Kidd
M S
MS
Kummer
A F
AF
Taylor
K
K
Kotze
U
U
Hanslo
D
D
D000328:Adult; D000349:Africa; D000368:Aged; D000369:Aged, 80 and over; D001426:Bacterial Proteins / Q000235:genetics; D016022:Case-Control Studies; D004269:DNA, Bacterial / Q000032:analysis; D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications* / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000209:etiology*; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; D004269:DNA, Bacterial