Prospective metabolomics investigation of gastric cancer risk in African Americans and European Whites with a low socioeconomic status

社会经济地位较低的非裔美国人和欧洲白人胃癌风险的前瞻性代谢组学调查

• 批准号: 10912190
• 负责人: Xiang Shu
• 金额: $ 30万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-22 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10912190
• 关键词: Accounting; African American; African American population; American; Antibodies; Antigens; Asian; Asian Americans; Asian population; Assessment tool; Biological; Biological Markers; Blood; Body mass index; Cancer Etiology; Cancer Patient; Cancer and Nutrition; Cessation of life; Chimeric Proteins; Coffee; Cohort Studies; Communities; Cytotoxin; Data; Development; Diagnosis; Diagnostic; Dietary intake; East Asian; Environmental Risk Factor; Etiology; European; Evaluation; Exposure to; Funding; Future; Goals; Green tea; Health; Helicobacter Infections; Helicobacter pylori; Hispanic; Hispanic Populations; Human; Individual; Infrastructure; Intake; International; Investigation; Latino; Latino Population; Low Prevalence; Malignant Neoplasms; Mediating; Mediation; Mexican Americans; Minority Groups; Neoplasm Metastasis; Nested Case-Control Study; Outcome; Pathway interactions; Patients; Pilot Projects; Plasma; Play; Population; Population Heterogeneity; Prevention; Process; Processed Meats; Progestins; Prospective cohort; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; Publishing; Race; Reporting; Research Activity; Research Design; Resources; Rest; Risk; Risk Assessment; Risk Factors; Role; SEER Program; Sampling; Screening for Gastric Cancer; Series; Smoking; Steroids; Stomach; Techniques; Time; United States; Validation; Vegetables; Vitamin B 12 Deficiency; Women' s Health; Work; biomarker validation; cancer biomarkers; cancer diagnosis; cancer risk; carcinogenesis; case control; cohort; demographics; design; design verification; disorder prevention; draining lymph node; drinking; epidemiologic data; gastric cancer prevention; gastric carcinogenesis; high risk population; improved; innovation; insight; lifestyle factors; low socioeconomic status; male health; malignant stomach neoplasm; metabolome; metabolomics; multi-ethnic; novel; novel marker; population based; prospective; racial minority population; response; screening; sex; specific biomarkers; steroid hormone; stomach cardia; tool; tumor progression

ABSTRACT Gastric cancer is one of the most common and deadly cancers globally, accounting for over one million new cancer diagnoses and 783,000 deaths in 2018. Infection of Helicobacter pylori (H. pylori) is the most important risk factor and a necessary cause for non-cardia gastric cancer. While targeting high-risk populations who are infected with H. pylori seems a compelling strategy for gastric cancer screening and prevention, a significant concern not addressed is that only ~1 to 3% of the H. pylori infected individuals develop gastric cancer, indicating that such strategy based on H. pylori status alone is insufficient, particularly among populations with a relatively low prevalence of H. pylori infection. Thus, discovering and validating additional biomarkers, especially non- invasive ones, are needed to facilitate the development of novel risk assessment tools for gastric cancer. The human metabolome reflects endogenous responses and processes to exposures, including environmental and lifestyle factors that are related to carcinogenesis. The use of advanced metabolomics techniques in prospective population-based cohort studies have successfully identified both novel etiologic factors and risk biomarkers for different cancers. However, few prior studies have focused on identifying novel risk biomarkers for gastric cancer using metabolomics techniques, particularly in prospective design settings. We recently conducted the first nested case-control study within two large prospective cohorts. Our study identified 5 metabolites associated with risk of gastric cancer after correction for multiple comparisons and 13 additional metabolite candidates for further investigations. These include metabolites related to vitamin B12 deficiency, green tea/coffee intake, and two progestin steroids, representing a few biologically plausible mechanisms involved in gastric cancer etiology. Herein, we propose to conduct a large prospective investigation within a newly formed international consortium to validate these highly promising findings, as well as discovering novel risk biomarkers, using both untargeted and targeted metabolomics approaches. Pre-diagnostic plasma samples and epidemiologic data including demographics, lifestyle factors, and dietary intakes will be harmonized for >1,600 incident cases and about 2,000 matched controls from eight prospective cohorts. The proposed study will incorporate a rigorous two-stage design to screen and validate circulating metabolite biomarkers for gastric cancer risk in Asians and Whites (Aim 1). We will further assess the generalizability of the validated biomarkers in Asian Americans, African Americans, and Hispanics/Latinos as well as discover novel race-specific biomarkers in these populations for future investigation (Aim 2). Finally, we will assess mediating effects of the identified metabolites on the associations between known risk factors and gastric cancer to facilitate the understanding of involved biological mechanisms (Aim 3). Through a series of rigorously designed research activities, fresh insights into mechanism of gastric carcinogenesis and novel biomarkers for future development of risk assessment tools are expected.

抽象的 胃癌是全球最常见，最致命的癌症之一，占新的癌症 2018年的癌症诊断和783,000人死亡。幽门螺杆菌的感染是最重要的 危险因素和非心脏胃癌的必要原因。同时针对高风险人群 被幽门螺杆菌感染似乎是胃癌筛查和预防的令人信服的策略，这是一个重要的 不关心的是，只有〜1至3％的幽门螺杆菌感染的个体患胃癌，表明 仅基于幽门螺杆菌状况的这种策略是不够的，尤其是在相对的人群中 幽门螺杆菌感染的患病率低。因此，发现和验证其他生物标志物，尤其是非 - 需要侵入性的，以促进胃癌的新风险评估工具的开发。这 人代谢组反映了内源性的反应和过程，包括环境和包括环境和 与癌变有关的生活方式因素。前瞻性的高级代谢组学技术的使用 基于人群的队列研究成功地确定了新的病因学因素和风险生物标志物 不同的癌症。但是，很少有研究重点是鉴定胃癌的新风险生物标志物 使用代谢组学技术，尤其是在潜在的设计环境中。我们最近进行了第一个 在两个大型前瞻性队列中的嵌套病例对照研究。我们的研究确定了5种相关的代谢产物 有多次比较后的胃癌风险，另外13个代谢物候选者 进一步调查。其中包括与维生素B12缺乏症，绿茶/咖啡摄入和 两种孕激素类固醇，代表了一些与胃癌病因有关的生物学上合理的机制。 在此，我们建议在新成立的国际财团内进行大规模的前瞻性调查 验证这些高度有希望的发现以及发现新型风险生物标志物的发现 和靶向代谢组学方法。诊断前血浆样本和流行病学数据，包括 人口统计学，生活方式因素和饮食摄入量将在> 1,600个事件案例中进行协调，约有2,000例 来自八个前瞻性队列的控件。拟议的研究将结合一个严格的两个阶段 筛选和验证亚洲人和白人胃癌风险的循环代谢物生物标志物的设计（目标 1）。我们将进一步评估经过验证的生物标志物在亚裔美国人，非裔美国人， 以及西班牙裔/拉丁美洲人，以及在这些人群中发现新颖的种族特异性生物标志物 调查（目标2）。最后，我们将评估已鉴定的代谢物对关联的中介作用 在已知的危险因素和胃癌之间，以促进对所涉及的生物学机制的理解 （目标3）。通过一系列严格设计的研究活动，对胃机制的新见解 预计可将未来开发的风险评估工具开发的癌变和新型生物标志物。