Early-onset colorectal cancer: initial clues and current views

Abstract

Over the past several decades, the incidence of early-onset colorectal cancer (EOCRC; in patients <50 years old) has increased at an alarming rate. Although robust and scientifically rigorous epidemiological studies have sifted out environmental elements linked to EOCRC, our knowledge of the causes and mechanisms of this disease is far from complete. Here, we highlight potential risk factors and putative mechanisms that drive EOCRC and suggest likely areas for fruitful research. In addition, we identify inconsistencies in the evidence implicating a strong effect of increased adiposity and suggest that certain behaviours (such as diet and stress) might place nonobese and otherwise healthy people at risk of this disease. Key risk factors are reviewed, including the global westernization of diets (usually involving a high intake of red and processed meats, high-fructose corn syrup and unhealthy cooking methods), stress, antibiotics, synthetic food dyes, monosodium glutamate, titanium dioxide, and physical inactivity and/or sedentary behaviour. The gut microbiota is probably at the crossroads of these risk factors and EOCRC. The time course of the disease and the fact that relevant exposures probably occur in childhood raise important methodological issues that are also discussed.

Fig. 1 |. The effect of the exposome and early-life environmental exposures on microbiome health.

Exposomal elements that modulate the gut microbiome include not only those elements meeting the four metrics discussed in this Review (such as stress, antibiotics and dietary factors; TABLE 1) but also elements previously thought to be disconnected from colon health, such as birth mode, breastfeeding behaviours and maternal stress and nutrition. In turn, given the role of the microbiome in disease genesis (and the role of the microbiome in maintaining gut health) it probably has a key role in guiding colonic health and development of colorectal cancer. This role might or might not be mediated by obesogenic pathologies. EOCRC, early-onset colorectal cancer; MSG, monosodium glutamate.

Fig. 2 |. Solutions for EOCRC.

To address the rise in early-onset colorectal cancer (EOCRC), solutions can be deployed now, deployed with additional work to overcome barriers and deployed with money, time, ingenuity and scientific rigour. CRC, colorectal cancer.