Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Cancer Epidemiol Biomarkers Prev. 2021 Sep;30(9):1634-1642. doi: 10.1158/1055-9965.EPI-20-1633. Epub 2021 Apr 1.
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.
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 values.
Eighteen metabolites were associated with gastric cancer risk at < 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; = 1.89 × 10). Levels of methylmalonate, a suggested biomarker of vitamin B12 deficiency, was correlated with increased gastric cancer risk (OR = 1.42; = 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.
Our study identified multiple potential risk biomarkers for gastric cancer independent of infection and other major risk factors.
New risk-assessment tools to identify high-risk population could be developed to improve prevention of gastric cancer..
代谢组学广泛用于识别癌症风险的潜在新型生物标志物。然而，尚未有研究前瞻性评估代谢组扰动在胃癌发展中的作用。
从上海女性健康和上海男性健康研究中选择了 250 例经确诊的原发性胃癌病例，并通过发病率密度抽样法为每个病例匹配 1 名对照。采用非靶向全局分析平台测量了约 1000 种预诊断血浆中的代谢物。利用条件逻辑回归生成 OR 和 值。
18 种代谢物与胃癌风险相关（ < 0.01）。其中，11 种代谢物为溶血磷脂或其他类别的脂质；例如，1-（1-烯基-棕榈酰基）-GPE（P-16：0）（OR=1.56； =1.89×10）。丙二酸单酯的水平与胃癌风险增加相关，丙二酸单酯是维生素 B12 缺乏的一种提示性生物标志物（OR=1.42； =0.004）。与咖啡/茶消费相关的三个生物标志物（3-羟基吡啶硫酸盐、奎宁酸和 N-（2-呋喃基）甘氨酸）呈负相关，但仅当将血液采集后 5 年内确诊的病例与匹配对照进行比较时，相关性才具有统计学意义。与男性或曾吸烟者相比，大多数确定的关联在女性和从不吸烟者中更为显著，其中一些关联具有显著的交互作用。
本研究确定了多个独立于 感染和其他主要危险因素的胃癌潜在风险生物标志物。
可以开发新的风险评估工具来识别高危人群，以改善胃癌的预防。
