Hepatocyte Growth Factor in Blood and Gastric Cancer Risk: A Nested Case-Control Study

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 29; no. 2; pp. 470 - 476
• Main Authors: Jang, Jieun, Ma, Seung Hyun, Ko, Kwang-Pil, Choi, Bo Yul, Yoo, Keun-Young, Park, Sue K
• Format: Journal Article
• Language: English
• Published: United States 01.02.2020
• Subjects: Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Antigens, Bacterial - immunology; Antigens, Bacterial - metabolism; Bacterial Proteins - immunology; Bacterial Proteins - metabolism; Biomarkers, Tumor - blood; Biomarkers, Tumor - metabolism; Case-Control Studies; Female; Follow-Up Studies; Helicobacter Infections - blood; Helicobacter Infections - diagnosis; Helicobacter Infections - microbiology; Helicobacter Infections - pathology; Hepatocyte Growth Factor - blood; Hepatocyte Growth Factor - metabolism; Humans; Male; Middle Aged; Models, Statistical; Polymorphism, Single Nucleotide; Predictive Value of Tests; Prospective Studies; Proto-Oncogene Proteins c-met - genetics; Proto-Oncogene Proteins c-met - metabolism; Risk Assessment - methods; Risk Factors; ROC Curve; Signal Transduction - genetics; Stomach Neoplasms - blood; Stomach Neoplasms - epidemiology; Stomach Neoplasms - microbiology; Stomach Neoplasms - pathology
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-19-0436

Potential of hepatocyte growth factor (HGF)-stimulating signaling pathways related to cytotoxin-associated gene A (CagA) to predict gastric cancer development has not been fully investigated. We conducted a nested case-control study consisting of 238 gastric cancer cases and 238 matched controls within the Korean Multicenter Cancer Cohort. Plasma HGF concentrations were measured with a human HGF ELISA. Odds ratios (OR) and 95% confidence intervals (CI) for gastric cancer development according to HGF level were calculated using conditional logistic regression model. Sequential elevation of gastric cancer risk according to HGF level increase was observed (OR, 10.99; 95% CI, 4.91-24.62) for highest quartile HGF (≥364 pg/mL) versus lowest quartile HGF (<167 pg/mL). A significantly increased gastric cancer risk associated with high HGF level measured even 6 or more years prior to cancer diagnosis was also found. The group with both high risk of HGF and CagA-related genetic variants was associated with highest gastric cancer risk compared with the group with both low risk of HGF and genetic variants ( = 0.05). Model performance using HGF and CagA-related genetic variants to discriminate gastric cancer 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. Our results suggest HGF as a potential biomarker to predict gastric cancer development. These findings suggest HGF as a useful biomarker to predict gastric cancer risk. Further research to assess gastric cancer risk based on useful biomarkers, including HGF, may contribute to primary prevention of gastric cancer.