Rising incidence of early-onset colorectal cancer - a call to action

Abstract

The incidence of early-onset colorectal cancer (CRC), which occurs in individuals <50 years of age, has been increasing worldwide and particularly in high-income countries. The reasons for this increase remain unknown but plausible hypotheses include greater exposure to potential risk factors, such as a Western-style diet, obesity, physical inactivity and antibiotic use, especially during the early prenatal to adolescent periods of life. These exposures can not only cause genetic and epigenetic alterations in colorectal epithelial cells but also affect the gut microbiota and host immunity. Early-onset CRCs have differential clinical, pathological and molecular features compared with later-onset CRCs. Certain existing resources can be utilized to elucidate the aetiology of early-onset CRC and inform the development of effective prevention, early detection and therapeutic strategies; however, additional life-course cohort studies spanning childhood and young adulthood, integrated with prospective biospecimen collections, omics biomarker analyses and a molecular pathological epidemiology approach, are needed to better understand and manage this disease entity. In this Perspective, we summarize our current understanding of early-onset CRC and discuss how we should strategize future research to improve its prevention and clinical management.

Figure 1.

Illustration of potential effects of various life-course exposures on tumor development from early life (the prenatal to adolescent periods) to adulthood. The exposome indicates the totality of exposures and interactions thereof. The gene-by-environment (GxE) interactions during life-course may play an important role in the etiology of early-onset colorectal cancer. Early-life biospecimens such as stool, blood, saliva, urine, cord blood, placenta, etc., which can be collected from either mother or fetus/neonate or both, may be able to provide early-life information when analyzed in the future. Abbreviations: GxE, gene-by-environment; wt, weight.