Behavioral Risk Factors and Risk of Early-Onset Colorectal Cancer: Review of the Mechanistic and Observational Evidence

Abstract

Purpose of the Review: The goal of this review is to summarize recent evidence linking behavioral risk factors to early-onset colorectal cancer (EO-CRC) as the incidence continues to rise by 2% annually in the USA. The potential mechanisms linking these risk factors to EO-CRC are also discussed. Recent Findings: Obesity and sedentary behavior have been associated with an increased risk of EO-CRC in women through a large cohort study, while the data is inconclusive for men. Diabetes was also associated with an increased risk of EO-CRC in a large Swedish cohort study. While the evidence for metabolic syndrome and diet comes from cross-sectional studies, they still point to an association with EO-CRC. The mechanisms underlying these risk factors include inflammation, gut dysbiosis, and aberrant mitogenic signaling. Summary: The etiology of EO-CRC likely involves a multifactorial mechanism that will require a multidisciplinary approach. Existing consortia and new data harmonization of multiple studies will be useful in re-evaluating the role of established lifestyle/genetic risk factors of CRC in EO-CRC. Future investigations should prospectively collect information on exposures and biospecimens, particularly during early life, to further elucidate risk factors and contributors to the rising incidence of EO-CRC.