Gut Microbiome, Antibiotic Use & Colon Cancer Recurrence

项目摘要/摘要 尽管在预防、筛查和治疗方面取得了进展，但结直肠癌(CRC)仍位居第三 年，在男性和女性中，常见癌症和癌症死亡的第二大原因加起来 美国。目前生活在美国的近120万儿童癌症幸存者面临着儿童疾病预后不良的风险。这个 大量的儿童权利公约幸存者，加上儿童权利委员会巨大的财政负担，使其成为至关重要的 确定可用于指导临床决策的预测结直肠癌患者复发的生物标志物 关于治疗和监测。目前还没有明确的生物标志物来识别结肠癌。 复发的可能性很高。人类的肠道含有世界上最大的细菌生态系统(肠道微生物组)。 人体。然而，肠道微生物群(直接或间接通过细菌代谢物)是否 与CRC复发相关的疾病尚不清楚。最后，考虑到抗生素的流行，而且经常是过度使用 和质子泵抑制剂(PPI)在人群中，以及它们对肠道微生物群的影响， 抗生素和PPI的使用与结直肠癌复发需要进行调查。为了解决这些知识差距， 拟议的研究试图产生高通量的16S测序数据来调查 肿瘤特异性肠道微生物谱与结肠癌复发的关系。这项研究将分两个阶段进行。 在发现阶段，我们将确定与283例结肠癌早期复发相关的细菌图谱。 II/III期患者有可用的Snap冰冻肿瘤组织。在验证阶段，排名靠前的候选细菌 从我们的发现阶段开始，将在一组独立的600名II/III期结肠癌患者中进行评估。 最后，利用丹麦医疗、临床和人口登记中的大量高质量数据， 我们将检查诊断前抗生素治疗和质子泵抑制剂(PPI)的使用是否相关 2001至2012年间在丹麦确诊的21,000例结直肠癌患者中出现复发。调查结果 我们的研究将有助于识别结肠癌复发的潜在肿瘤特异性生物标记物， 并阐明肠道微生物组在结肠癌进展中的可能作用。

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.