Gut Microbiome, Antibiotic Use & Colon Cancer Recurrence

肠道微生物组、抗生素的使用

• 批准号: 9751802
• 负责人: Veronika Fedirko
• 金额: $ 49.7万
• 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/9751802
• 关键词: 16S ribosomal RNA sequencing; 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; Consensus; Coupled; Data; Data Quality; Denmark; Diagnosis; Diagnostic; Distal; Ecosystem; Ethnic Origin; Exposure to; Financial Hardship; Freezing; Fusobacterium; Genes; Goals; High-Throughput Nucleotide Sequencing; Human; Human Genome; Human body; Individual; Knowledge; Medical; 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; bacterial community; base; cancer diagnosis; cancer recurrence; clinical biomarkers; clinical decision-making; colon cancer patients; colon cancer progression; colorectal cancer progression; design; gut microbes; gut microbiome; high risk; improved; interest; mRNA sequencing; men; microbial; microbiota profiles; molecular subtypes; neoplasm registry; outcome forecast; prospective; 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.

项目摘要/摘要 尽管预防，筛查和治疗取得了进步，但结直肠癌（CRC）仍然是第三大多数 通常被诊断为癌症和男性和女性癌症死亡的第二大原因 美国。目前居住在美国的近120万CRC幸存者处于不良CRC结果的危险中。这 大量的CRC幸存者加上CRC的巨大经济负担，至关重要 确定可预测可用于指导临床决策的CRC患者复发的生物标志物 关于治疗和监视。目前没有确定的生物标志物可以鉴定出与 复发的可能性很大。人类肠道中包含最大的细菌生态系统（肠道微生物组） 人体。但是，肠道微生物组（直接或间接通过细菌代谢物）是 与CRC复发相关的是未知的。最后，考虑到抗生素的患病率，经常过度使用 人群中的质子泵抑制剂（PPI）及其对肠道微生物组的影响 需要研究抗生素和PPI与CRC复发一起使用。为了解决这些知识差距， 拟议的研究旨在生成高通量16S测序数据，以研究 肿瘤特异性肠道微生物谱，具有结肠癌复发。这项研究将分为两个阶段。 在发现阶段，我们将确定283个结肠癌的早期复发相关的细菌特征 II/III期患者，具有可用的SNAP冷冻肿瘤组织。在验证阶段，顶级细菌候选者 从我们的发现阶段将在独立的600阶段II/III结肠癌患者中进行评估。 最后，利用丹麦医学，临床和人口登记处的大量高质量数据， 我们将检查诊断前抗生素疗法和质子泵抑制剂（PPI）是否相关 在2001年至2012年在丹麦诊断出的> 21,000名CRC患者之间的复发。发现 我们的研究将有助于鉴定结肠癌复发的潜在肿瘤特异性生物标志物， 并阐明肠道微生物组在结肠癌进展中的可能作用。