Colorectal cancer (CRC) is the second leading cause of cancer death in men and women combined in the U.S., discount viagra affecting one in every 20 individuals (1). Although it is considered a “Western” disease, the incidence is increasing worldwide. CRC has long been recognized as genetic disease, and follows an “adenoma-carcinoma” model developing as mutations accumulate (2). The genes most commonly mutated in CRC include adenomatous polyposis coli (APC), b-catenin (CTNNB1), P53, Kirsten rat sarcoma oncogene (KRAS), and myelocytomatosis oncogene (MYC) (3). These are driver mutations associated with several cancer hallmarks: uncontrolled cell growth and replication, resistance to apoptosis, angiogenesis, tissue invasion and metastasis, reprogramming of energy metabolism, evading immune destruction, and inflammation (4).
The advancement in microbial identification and human microbiome studies have revolutionized our view of the microorganisms associated with disease, including CRC. Using various “omics” approaches, a number of studies have consistently identified Fusobacterium nucleatum to be highly enriched in colorectal carcinomas (5–8). A subsequent study reported that F. nucleatum was not only enriched in CRC, but also in benign precancerous polyps (9). F. nucleatum, a gram-negative anaerobe, is one of >600 microbial species inhabiting the human oral cavity, implicated in periodontal disease (10, 11). Increasing evidence suggests that oral bacteria are not confined to the oral cavity, and can migrate to extra-oral sites causing infections and inflammation (12). F. nucleatum has been isolated from a wide range of organ abscesses and infections, although it is never or rarely detected in those floras under normal conditions. For example, this organism is capable of crossing the placental barrier, causing pregnancy complications such as preterm birth, stillbirth and neonatal sepsis (12). Given that the oral cavity is at the beginning of the digestive tract, it is not surprising that microbial species find their way down the path. However, detection of F. nucleatum in the colorectal adenomas and carcinomas does not prove causality. Our study aims to address this issue and determine if F. nucleatum is indeed a driver of CRC (13).
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