Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths in the United States. When CRC is detected early, the 5-year relative survival rate is 90%. However, only 37% of CRC cases are detected at an early stage and the 5-year survival rate for subjects presenting with distant metastases is only 8-9%. While colonoscopy has reported sensitivity and specificity values exceeding 95%, the degree of adherence is low due to the cost, as well as to perceived inconvenience and discomfort associated with this test. As a result, many patients still present with late-stage and potentially fatal disease. Although many blood- or stool-based tests for CRC have been developed in recent years, none of these tests have sensitivity and specificity similar to those of colonoscopy. Thus, there continues to be an important need for the development of a simple, non-invasive and highly reliable test for the early detection of CRC. We have found that plasma levels of several lysophosphatidylcholines (LPCs) are potential markers for CRC and in our pilot work we show that these markers achieved a sensitivity and specificity of 82% and 93%, respectively for CRC. It is critical and absolutely necessary to establish reproducibility and to retest and validate the estimates for sensitivity and specificity in completely independent sample sets in order to critically evaluate the clinical significance and utility of these markers. In addition, it is important to determine whether LPCs are changed in adenomatous polyps. We propose two aims. First, we will determine whether LPCs are effective markers for detecting CRC by determining their sensitivity and specificity in a totally independent study. 174 pairs of blood samples from CRC cases and colonoscopic negative controls will be analyzed. Secondly, will will determine whether plasma levels of LPCs are markers for early colorectal neoplasia and/or disease progression. We will determine whether plasma LPCs are reduced in subjects with adenomatous polyps (194 samples), as compared to colonoscopically negative healthy controls, and whether the levels of LPCs correlate with the size and histo-pathology of adenomatous polyps. These studies will provide critical information to evaluate the potential of LPCs'clinical usage. PUBLIC HEALTH RELEVANCE: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths in the United States. There continues to be an important need for the development of a simple, non-invasive and highly reliable test for the early detection of CRC, since when CRC is diagnosed at an early stage, it is curable. We have found that a group of lipid compounds called lysophosphatidylcholines (LPCs) may represent useful markers for the early detection of CRC. The proposed studies will critically evaluate and validate these markers in healthy control subjects, patients with adenomatous polyps, and patients with colorectal cancers.