Emerging trends in the global burden of colorectal cancer.

Globally, colorectal cancer (CRC) is the third most frequently diagnosed cancer and the second leading cause of cancer-related deaths, although these epidemiological patterns show substantial geographical variation. In this Review, we discuss the emerging global patterns of CRC incidence, which historically has been the highest among Western, high-income countries but is now increasing globally beyond these regions. This rise has mainly been driven by early-onset CRC - that is, cancers diagnosed in individuals aged <50 years. A birth cohort effect beginning with individuals born in the 1960s indicates that factors beyond genetic susceptibility or changes in screening practice underlie this increase. A changing landscape of established and emerging risk factors occurring worldwide has been proposed to underlie these epidemiological trends in CRC. Hypothesized risk factors include dietary and lifestyle aspects, shifts in the gut microbiota and the rise in environmental contaminants associated with the rapid urbanization occurring globally. Substantial advances in the characterization of genomic and epigenomic profiles of CRCs as well as their gut microbiomes not only hold potential for providing insight on the aetiology of this disease but could also be leveraged for early detection and interception strategies. The under-representation of non-Western populations in these studies, however, greatly limits progress and, if not addressed, could widen the existing gaps in global CRC prevention and control.