Figure 2. Hypothesized sporadic normal-to-adenoma-to-carcinoma progression in the colon for early onset colorectal cancer. A presumed environmental trigger in the microenvironment milieu helps create the conditions that trigger early existing and/or initiating genetic and epigenetic alterations that begin to propel a normal colonocyte or colon stem cell towards excessive proliferation. After neoplastic initiation, the local microenvironment intermittently or constantly continues to provide the conditions to propel further genetic and epigenetic alterations that are manifested by histologic changes, ultimately accumulating sufficient genomic changes to define it as a cancer and acquiring the capability of metastatic spread. The local microenvironment is highly influenced by diet and diet supplements, tobacco and alcohol use, aspirin and NSAID use, and metabolic pathways important in obesity regulation. Within the local microenvironment are multiple factors that may indirectly or directly influence epithelial behavior, including the makeup of the gut microbiome and its metabolites and toxins, levels and types of inflammatory cells, presence of oxygen and free radicals, and other potential carcinogens.