Global metabolomics profiling, dietary factors, and colorectal cancer risk in the NIH-Consortium of Metabolomics Studies (COMETS)

NIH 代谢组学研究联盟 (COMETS) 中的全球代谢组学分析、饮食因素和结直肠癌风险

• 批准号: 10645028
• 负责人: Mary Christine Playdon
• 金额: $ 7.47万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-14 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10645028
• 关键词: Address; Age; Alcohols; Asia; Biological Assay; Biological Markers; Biology; Blood; Blood specimen; Body mass index; Cancer Etiology; Chemicals; Clinical; Clinical Data; Collection; Colon; Colorectal Cancer; Consumption; Data; Data Set; Diagnosis; Diagnostic; Diet; Dietary Assessment; Dietary Factors; Dietary Fiber; Dietary intake; Disease; Ensure; Environment; Etiology; Europe; Female; Fishes; Food; Frequencies; Funding; Future; Goals; Heterogeneity; In Vitro; Incidence; Investigation; Laboratories; Link; Lipids; Location; Logistic Regressions; Malignant Neoplasms; Measurement; Mediating; Mediation; Metabolic; Metabolic Pathway; Metadata; Methods; Modeling; Names; Nested Case-Control Study; Nutritional; Obesity; Pathway interactions; Patient Self-Report; Physical activity; Play; Population; Population Heterogeneity; Preparation; Prevalence; Processed Meats; Prospective Studies; Prospective cohort; Prospective, cohort study; Public Health; Publishing; Questionnaires; Rectum; Research; Risk; Risk Factors; Role; Sex Differences; Site; Smoking; Standardization; Statistical Data Interpretation; Subgroup; Testing; Time; United States; United States National Institutes of Health; United States Preventative Services Task Force; Validation; Vegetables; Work; anticancer research; aqueous; biomarker identification; blood-based biomarker; cancer biomarkers; cancer diagnosis; case control; clinical application; cohort; colorectal cancer prevention; colorectal cancer risk; data integration; design; diet and cancer; dietary; epidemiologic data; experience; improved; in vivo; innovation; lifestyle factors; liquid chromatography mass spectrometry; male; metabolomics; novel; novel marker; prospective; rectal; risk prediction; screening; sex; stem; study population; tumor

Summary The prevalence of colorectal cancer (CRC) continues to increase worldwide and it remains the third most commonly diagnosed cancer in the United States. An enhanced understanding of CRC etiology is essential to develop tailored risk prediction methods. Metabolomics, the comprehensive study of small metabolites, is a promising approach to discover etiological biomarkers for CRC. Metabolomics analysis in combination with information on dietary intake could be used for the identification of objective dietary biomarkers for CRC. However, precise metabolic biomarkers to predict CRC are missing. To date, there are no objective dietary biomarkers for CRC risk and the biology underlying the relationship between diet and CRC remains poorly understood. The goal of the proposed work is to investigate associations of metabolites with CRC risk and to enhance our understanding of the underlying biology of the diet-CRC relationship. To achieve this goal, we will use existing global metabolomics data generated in three state-of-the art laboratories using pre-diagnosis biospecimens from eight independent, prospective cohorts from the US, Europe, and Asia. These well- annotated and unique datasets include data from n=3,085 matched case-control pairs from diverse populations, and thus ensure broad generalizability and clinical applicability of identified biomarkers. Data are integrated in the NIH-funded Consortium of Metabolomics Studies (COMETS) together with standardized and validated food frequency questionnaires (FFQ), and epidemiologic and clinical data. We will discover and validate novel blood-based metabolic biomarkers for CRC risk (Aim 1) in a discovery set of n=1,900 matched case-control pairs. Findings will be confirmed in an independent validation set including n=1,185 matched case-control pairs. Additionally, we will perform stratified analyses by sex, tumor location, and age at diagnosis to advance our understanding of CRC etiology across distinct subtypes. Using the described datasets, we will discover and validate correlations of food groups with metabolites. We will perform mediation analysis for the top performing diet-metabolite correlations to investigate the indirect effect of diet on CRC risk through metabolites (Aim 2). The proposed research is highly innovative in that it uses a rigorous multi-step design, employs for the first time a broad set of metabolic biomarkers (n~381) and dietary information, from highly characterized cohorts with biospecimens and questionnaires collected before cancer diagnosis, thus, protecting against reverse causation. Our interdisciplinary team has extensive experience in using metabolomics in cancer research and leverages substantial preliminary data. We expect that our investigation will discover and validate novel CRC biomarkers and enhance our understanding of the underlying biology of diet in CRC etiology, thus addressing a clearly defined clinical and public health need.

总结