Helicobacter pylori vacuolating cytotoxin genotypes and preneoplastic lesions or gastric cancer risk: a meta-analysis

Background and AimDisease progression to gastric cancer (GC) occurs in only a small proportion of Helicobacter pylori (H.pylori) infected patients. The bacterium vacuolating cytotoxin A (vacA) gene polymorphisms may determine the clinical consequences. We examined the strength of this association in adult-infected populations and modeled the impact of mean age-standardized incidence rates (ASRs) of GC as a hypothesized moderator variable. MethodsPooled relative risk (RR) estimates were calculated. Subgroup, sensitivity, and meta-regression analyses were conducted. ResultsTotally, 33 studies (1446 cases/2697 controls) were analyzed. The vacA-s1 genotype was significantly associated with an increased risk of atrophic gastritis(AG), intestinal metaplasia(IM), and GC (RR=1.116, 95% CI, 1.019-1.222; RR=1.418, 95% CI, 1.035-1.942; and RR=1.333, 95% CI, 1.115-1.593, respectively); however, the vacA m1 genotype strongly increased the risk of IM and GC, but not AG (RR=1.571, 95% CI, 1.247-1.980 and RR=1.431, 95% CI, 1.180-1.735, respectively). The vacA s1m1 allelic combination was linked to an increased risk of GC. The m1-type of vacA was more potent than s1 for predicting the risk of GC within the subgroups with the mean ASRs of 11/100000-19/100000 and less than 10/100000. The meta-regression analysis indicated that the ASR of GC modified the association between H.pylori genotypes and GC risk, where the estimated risk was significantly decreased with increasing the mean ASRs of GC (P-values=0.025, 0.00009, and 0.0005 for s1, m1, and s1m1, respectively). ConclusionsThe H.pylori vacA-s1 and vacA-m1 allelic variants strongly increased susceptibility to IM and GC; however, only s1 showed an association with AG. These associations were largely influenced by geographic variations in the GC incidence rate.