Positron Emission Tomography and Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer in the United States with > 135,000 cases reported every year and a life-time risk of 5–6%. It is the second leading cause for cancer-related death in the western world. Although 80% of CRC cases are sporadic, in 20% of patients a hereditary predisposition exists. Several genetic mutations have been implicated in an increased risk for developing CRC. In familial polyposis coli, there is a mutation of the adenomatous polyposis coli (APC) gene on chromosome 5. Mutations in the genes responsible for repair of mismatched DNA base pairs (mismatch repair genes) are the major cause of cancers in hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome), the most common hereditary form of CRC, accounting for up to 5% of CRC cases (Giardiello et al., 2001). Patients with inflammatory bowel disease are also at an increased risk for the development of CRC, up to 2–8 times greater than the risk for the general population. This risk is related to the duration and anatomic extent of inflammatory disease, and coexistence of primary sclerosing cholangitis (Vagefi and Longo, 2005). Population studies have associated advanced age, certain diets (low fiber, high fat, and red meat intake), smoking, alcohol consumption, and obesity with the development of CRC; however, a cause and effect link has not been proven for these factors.

There is compelling epidemiological, clinicopathological and genetic evidence for an adenoma-carcinoma sequence in the development of most CRC's. The adenoma-carcinoma sequence refers to the development of CRC from adenomatous polyps. The likelihood of malignancy developing in an adenoma is directly related to its size, volume of villous tissue, and the severity of epithelial dysplasia. Multiple underlying molecular and genetic changes along the adenoma-carcinoma sequence have been identified. For example, an imbalance in genomic DNA methylation may lead to oncogene activation (hypomethyla-tion) and silencing of tumor suppression genes (hypermethylation) (Hardy et al., 2000). The average estimated “dwell time” for an adenoma to transform into cancer is 10–15 years. However, not all adenomas progress to carcinomas, some may even spontaneously regress. Furthermore, many researchers believe that de novo carcino-genesis is a plausible alternate pathway to CRC development (Watanabe and Muto, 2000).