Helicobacter pylori infection and gastric cancer risk: evaluation of 15 H. pylori proteins determined by novel multiplex serology.

Infection with Helicobacter pylori is a major cause of gastric cancer (GC). The association likely has been underestimated in the past due to disease-related clearance of the infection. On the other hand, only a minority of the infected individuals develop GC, and better risk stratification is therefore highly desirable. We aimed to assess the association of GC with antibodies to 15 individual H. pylori proteins, determined by novel multiplex serology, to identify potentially relevant risk markers. This analysis was based on 123 GC cases aged 50 to 74 years and 492 age-matched and sex-matched controls from Saarland, Germany. Eight of the antibodies were significantly associated with noncardia GC and seven of them were significantly related to GC at any site. More pronounced associations were observed for noncardia GC; adjusted odds ratios (95% confidence intervals) ranged from 1.60 (1.01-2.54) for HyuA to 5.63 (3.20-9.91) for cytotoxin-associated antigen A (CagA). A dose-response relationship was found between the number of seropositivities and GC (P < 0.001). The seropositivities of CagA and GroEL were found to be independent predictors of GC, which were strongly related to GC risk in a dose-response manner (P < 0.001). In conclusion, GroEL was identified as a new independent risk marker that may contribute to enhanced quantification of H. pylori-related GC risk.