To our knowledge, this is the largest study (n = 360) investigating the distribution of the
H. pylori virulence
tnpA, tnpB and
cagA in dyspeptic patients. In the first study on
tnpA and
tnpB by Matter
et al.[
11], 63% of 215 clinical
H. pylori isolates were
tnpA positive and 13.5% were positive for
tnpB, with a statistically significant association between peptic ulcer disease (PUD) and
tnpA positive strains. This association was not apparent for
tnpB. In the current study there was a similar prevalence of
tnpA and
tnpB [171/360; 47.5% and 47/360; 13.1%, for
tnpA and
tnpB respectively], and a similar association between
cagA and gastric cancer patients as observed in a preliminary study by Matter
et al.[
11]. Unfortunately in their study the associations of
tnpA and
tnpB with
H. pylori associated disease types were not determined. In a more recent but smaller study Matter
et al. investigated associations between presence of
tnpA and
tnpB and gastric cancer in Brazilian patients with gastric cancer (n = 34) and gastritis (n = 34) [
17]. The patient population studied here is from the North of Iran (state of Mazandaran), and has been reported to not only have a very high
H. pylori infection rate but also a very high rate patients suffering from
H. pylori induced disease [
18] This high
H. pylori prevalence facilitates the collection of a large number of strains from a well defined, small geographical region and this facilitated a study on the putative association between the presence of tnpA/B and the clinical outcome of the
H.pylori infection. The prevalence of
tnpA and
tnpB among gastric cancer and gastritis patients in the Iranian population included in the current study was 42.1% and 60.0% for
tnpA, and 16.8% and 15.4% for
tnpB, respectively, which, again, was comparable to the findings in the Brazilian population with gastric cancer or gastritis (29.4% and 73.5% for
tnpA; and 2.9% and 5.9% for
tnpB, respectively). Kersulyte
et al.[
19] also reported a higher frequency of
tnpA in Peruvian gastric cancer strains than in gastritis strains (9/14 (46%) versus 15/45 (33%), respectively). Although the observed associations between
tnpA and gastric cancer are similar in the populations in Peru, Brazil and Iran [
11,
19], there are striking differences for associations of
cagA with disease status between these populations. We observed a clear association between the presence of
cagA and gastric cancer in the Iranian population, while Matter
et al.[
11] did not observe such an association in Brazil. While most studies report an association between the presence of
cagA and gastric cancer some studies do not observe this association [
20,
21]. In this particular case it may be due to the low number of patients included in their study (n = 64; versus 160 in our study). After the recognition of
H. pylori as an important gastric pathogen [
21], many attempts have been made to identify
H. pylori virulence factors predicting clinical outcome as this might assist physicians in prediction of disease progression [
22]. When using the gastritis group as controls for gene distribution we observed an increased prevalence of the
tnpA and
cagA genes in the gastric cancer group. To our knowledge this study represents the largest cohort tested thus far for the prevalence of
tnpA for an association with the various
H. pylori infection associated disease groups. While it is tempting to conclude from the increased prevalence of
tnpA and
cagA in the gastric cancer group that these genes may serve as useful biomarkers for gastric cancer one cannot draw that conclusion from a cross-sectional study like ours. Also our study design did not include a questionnaire on the disease history of our patients and hence we are unable to correlate clinical symptoms such as bleeding, reflux, abdominal pain etc. with the presence/absence of these virulence factors. A large prospective cohort study would be required to establish reliable positive and negative predictive values of these putative biomarkers. Due to the long time between infection and cancer development such a study would require long follow-up times, and since only few infected individuals develop cancer a large study cohort would be required. In addition there are ethical issues with such a study as the hypothesis to be tested is that patients infected with
tnpA positive
H. pylori strains are more prone to developing gastric cancer than patients infected with
tnpA negative strains. In order to test this hypothesis one must establish the presence of the
tnpA
+/−
H. pylori strain at the start of the study while refraining from eradication of these potentially carcinogenic strains for a long period of time. In spite of the shortcomings of our cross-sectional study it provides strong indications for the clinical relevance of the
tnpA gene of
H. pylori strains isolated from the Iranian population where the prevalence of
H. pylori is relatively high [
13] and this high prevalence is coupled to a high incidence of
H. pylori induced peptic ulcer disease and gastric cancers [
23]. In conclusion
tnpA but not
tnpB is clearly associated with a more severe disease outcome of
Hc pylori infections. As such
tnpA could be a valuable novel biomarker but clearly further studies are required to confirm these results especially since at present no obvious biological explanation for a GC inducing function of this putative transposase can be provided.