Environmental Exposure and Tumor Heterogeneity in Colorectal Cancer Risk and Outcomes

Colorectal cancers are a group of heterogeneous disorders that involve interactions among environmental influences, germ-line susceptibility factors, and accumulated genetic and epigenetic changes in the colorectal epithelium. This review provides background on environmental exposure and molecular pathways during colorectal cancer pathogenesis. Additionally, the review discusses the interplay between these risk factors in the context of colorectal cancer development and progression. Smoking, obesity, and regular aspirin use appear to have profound effects on colorectal cancer initiation and prognosis through the activation of pathways targeting gene methylation, inflammation, insulin mitogenesis, and cell proliferation. New data on other types of exposure and molecular changes will continue to improve our understanding of the cause of colorectal cancer, leading to novel therapeutic and preventive strategies and ultimate reduction in disease burden.