Multiple gene status in Helicobacter pylori strains and risk of gastric cancer development.
OBJECTIVE
The identification of the vacA intermediate region has provided new insights into the role of vacA heterogeneity in relation to gastro-duodenal pathogenesis. The aim of this study was to assess vacA polymorphism in Iranian Helicobacter pylori strains and its association with cagA as a major virulence determinant, gastric histopathology and disease.


METHODS
vacA polymorphism and serum antibody responses were studied in 207 H. pylori-infected (139 NUD, 34 PUD, and 34 GC) patients and correlated with gastric histopathology.


RESULTS
Multivariate logistic regression analysis found intermediate region typing superior to signal or mid region typing for screening high risk patients. vacA i1 allele was identified as an independent predictor of dysplasia (OR = 9.044; 95% CI: 1.11-73.33). Possession of s1/i1/cagA(+) strains was also identified as a predictor of intestinal metaplasia (OR = 3; 95% CI: 1.13-7.95), dysplasia (OR = 9.9; 95% CI: 1.23-80.86) and risk of GC (OR = 6.9; 95% CI: 2.5-18.66) as well as induction of anti-VacA sero-positivity (OR = 5.04; 95% CI: 1.8-13.6). Anti-VacA serology correctly detected 83.8% of s1/i1/cagA(+) strains carried by high-risk patients.


CONCLUSIONS
The current study emphasizes the implication of vacA polymorphic structure, especially the s1/i1/cagA(+) genotype, in increasing the risk of GC by revealing their association with gastric pre-neoplastic changes and their reflection in VacA sero-positivity which encourages the application of noninvasive procedures in population screening.
Douraghi
Masoumeh
M
Helicobacter pylori Research Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Talebkhan
Yeganeh
Y
Zeraati
Hojjat
H
Ebrahimzadeh
Fatemeh
F
Nahvijoo
Azin
A
Morakabati
Arman
A
Ghafarpour
Masoud
M
Esmaili
Maryam
M
Bababeik
Maryam
M
Oghalaie
Akbar
A
Rakhshani
Nasser
N
Hosseini
Mahmoud Eshagh
ME
Mohagheghi
Mohammad Ali
MA
Mohammadi
Marjan
M
D000230:Adenocarcinoma / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D004415:Dyspepsia / Q000276:immunology / Q000382:microbiology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications* / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D010437:Peptic Ulcer / Q000276:immunology / Q000382:microbiology; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000276:immunology / Q000382:microbiology* / Q000473:pathology
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; C074689:VacA protein, Helicobacter pylori