Gut Microbiome, Antibiotic Use & Colon Cancer Recurrence

肠道微生物组、抗生素的使用

• 批准号: 9384255
• 负责人: Veronika Fedirko
• 金额: $ 55.01万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9384255
• 关键词: Address; Age; Anatomy; Antibiotic Therapy; Antibiotics; Bacteria; Biological Markers; Cancer Etiology; Cancer Patient; Cancer Survivor; Cessation of life; Clinical; Colon; Colon Carcinoma; Colonic Neoplasms; Colorectal Cancer; Communities; Consensus; Coupled; Data; Data Quality; Denmark; Diagnosis; Diagnostic; Distal; Ecosystem; Ethnic Origin; Exposure to; Freezing; Fusobacterium; Genes; Goals; High-Throughput Nucleotide Sequencing; Human; Human Genome; Human body; Individual; Knowledge; Medical; Messenger RNA; Operative Surgical Procedures; Outcome; Pathologic; Pathway interactions; Patient Recruitments; Patients; Pharmaceutical Preparations; Phase; Physiology; Play; Population; Prevalence; Prevention; Prevention strategy; Proton Pump Inhibitors; Public Health; Race; Rectal Cancer; Recurrence; Registries; Risk; Role; Sampling; TNM; Tumor Markers; Tumor Tissue; Universities; University Hospitals; Validation; Woman; base; cancer diagnosis; cancer recurrence; clinical biomarkers; clinical decision-making; colon cancer patients; design; gut microbiome; high risk; improved; interest; men; microbial; microbiota; molecular subtypes; neoplasm registry; outcome forecast; prospective; rRNA Genes; screening; sex; tertiary prevention; transcriptome; transcriptome sequencing; tumor; tumor microenvironment; tumor progression

PROJECT SUMMARY/ABSTRACT Despite advances in prevention, screening, and treatment, colorectal cancer (CRC) remains the 3rd most commonly diagnosed cancer and the 2nd leading cause of cancer deaths among men and women combined in the US. Nearly 1.2 million CRC survivors currently living in the US are at risk of adverse CRC outcomes. The large number of CRC survivors coupled with the considerable financial burden of CRC makes it critical to identify biomarkers to predict recurrence among CRC patients that can be used to guide clinical decisions regarding treatment and surveillance. Currently there are no definitive biomarkers to identify colon cancer with a high likelihood to recur. The human gut contains the largest bacterial ecosystem (gut microbiome) in the human body. However, whether the gut microbiome (directly or indirectly via bacterial metabolites) is associated with CRC recurrence is unknown. Lastly, given the prevalence, and often overuse, of antibiotics and proton pump inhibitors (PPIs) in the population, and their effects on the gut microbiome, the association of antibiotic and PPI use with CRC recurrence needs to be investigated. To address these knowledge gaps, the proposed study seeks to generate high-throughput 16S sequencing data to investigate the associations of tumor-specific gut microbial profiles with colon cancer recurrence. This study will be conducted in two phases. In the discovery phase, we will identify bacterial profiles associated with early recurrence in 283 colon cancer stage II/III patients with available snap frozen tumor tissue. In the validation phase, top bacterial candidates from our discovery phase will be evaluated in an independent set of 600 stage II/III colon cancer patients. Finally, taking advantage of a wealth of high-quality data in Danish medical, clinical, and population registries, we will examine whether pre-diagnostic antibiotic therapy and proton pump inhibitor (PPI) use are associated with recurrence among >21,000 CRC patients diagnosed between 2001 and 2012 in Denmark. The findings of our study will contribute to identification of potential tumor-specific biomarkers of colon cancer recurrence, and clarify the possible roles of the gut microbiome in colon cancer progression.

项目总结/文摘