Hepatocyte growth factor in blood and gastric cancer risk: a nested case-control study

Background: Potential of hepatocyte growth factor (HGF) stimulating signaling pathways related to cytotoxin-associated gene A (CagA) to predict GC development has not been fully investigated. Methods: We conducted a nested case-control study consisting of 238 GC cases and 238 matched controls within the Korean Multicenter Cancer Cohort. Plasma HGF concentrations were measured with a human HGF enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) for GC development according to HGF level were calculated using conditional logistic regression model. Results: Sequential elevation of GC risk according to HGF level increase was observed (OR, 10.99; 95% CI, 4.91-24.62 for highest quartile HGF (≥364 pg/mL) vs. lowest quartile HGF (<167 pg/mL). A significantly increased GC risk associated with high HGF level measured even 6 or more years prior to cancer diagnosis was also found. Group with both high risk of HGF and CagA-related genetic variants was associated with highest GC risk compared to group with both low risk of HGF and genetic variants (p-interaction = 0.05). Model performance including HGF and CagA-related genetic variants to discriminate GC was fair (area under the curve of receiver operating characteristic (AUC-ROC), 0.71; 95% CI, 0.64-0.78) and significantly higher than that of model not including those biomarkers. Conclusions: Our results suggest HGF as a potential biomarker to predict GC development. Impact: These findings suggest HGF as a useful biomarker to predict GC risk. Further research to assess GC risk based on useful biomarkers including HGF may contribute to primary prevention of GC.