A Prospective Investigation of Circulating Metabolome Identifies Potential Biomarkers for Gastric Cancer Risk

Background: Metabolomics is widely used to identify potential novel biomarkers for cancer risk. No investigation, however, has been conducted to prospectively evaluate the role of perturbation of metabolome in gastric cancer development. Methods: 250 incident cases diagnosed with primary gastric cancer were selected from the Shanghai Women’s Health and the Shanghai Men’s Health Study, and each was individually matched to one control by incidence density sampling. An untargeted global profiling platform was used to measure approximately 1,000 metabolites in prediagnostic plasma. Conditional logistic regression was utilized to generate ORs and P values. Results: Eighteen metabolites were associated with gastric cancer risk at P < 0.01. Among them, 11 metabolites were lysophospholipids or lipids of other classes; for example, 1-(1-enyl-palmitoyl)-GPE (P-16:0) (OR = 1.56; P = 1.89 × 10–4). Levels of methylmalonate, a suggested biomarker of vitamin B12 deficiency, was correlated with increased gastric cancer risk (OR = 1.42; P = 0.004). Inverse associations were found for three biomarkers for coffee/tea consumption (3-hydroxypyridine sulfate, quinate and N-(2-furoyl) glycine), although the associations were only significant when comparing cases that were diagnosed within 5 years after the blood collection to matched controls. Most of the identified associations were more profound in women and never smokers than their male or ever smoking counterparts and some with notable significant interactions. Conclusions: Our study identified multiple potential risk biomarkers for gastric cancer independent of Helicobacter pylori infection and other major risk factors. Impact: New risk-assessment tools to identify high-risk population could be developed to improve prevention of gastric cancer. See related commentary by Drew et al., p. 1601