Helicobacter pylori serological biomarkers of gastric cancer risk in the MCC-Spain case-control Study

•H. pylori antibody reactivity pattern is related to non-cardia gastric cancer risk.•Combined high seroreactivities for several H. pylori proteins could identify a decreased risk.•Cagδ seropositivity was independently associated with a lower risk.

BackgroundHelicobacter pylori infection is one of the main risk factors for non-cardia gastric cancer. However, only a minority of infected persons develop the disease. This study aims at identifying H. pylori related serological biomarkers of risk for gastric cancer.MethodsIncident gastric cancer cases and population controls (age, sex and region frequency-matched) from the MCC-Spain multicase-control Study were included. Seroreactivities against 16 H. pylori proteins were determined using multiplex serology. Infection was defined as seropositivity against ≥ 4 proteins. Relation of serological results to non-cardia and cardia gastric cancer was assessed using multivariable mixed logistic regression and principal components analysis.ResultsSeroprevalence was 88% among 2071 controls, 95% among 202 non-cardia gastric cancer cases (OR = 1.9 (95% CI: 1.0-3.6)) and 85% among 62 cardia cancer cases (OR = 0.5 (95% CI: 0.3-1.1)). In infected subjects, seropositivity for UreA, HP231, NapA and Cagδ was associated with lower non-cardia gastric cancer risk, while seropositivity for CagA and VacA was associated with higher risk. Seropositivity for CagA and seronegativity for Cagδ maintained the association after additional adjustment by serostatus of significant proteins. We identified two antibody reactivity patterns: the “virulent-pattern”, related to a threefold higher risk of non-cardia gastric cancer and the “non-virulent pattern”, related to a 60% decreased risk (4th vs. first quartile).ConclusionsIn our population, people seropositive for H. pylori were characterized by two patterns of antibody reactivity against H. pylori proteins: 1) Combined high seroreactivity against several proteins, associated with a lower non-cardia gastric cancer risk, and 2) High seroreactivity against CagA and VacA, associated with an increased risk.